Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 90
Filter
1.
Ann Oncol ; 21(4): 707-716, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19815652

ABSTRACT

BACKGROUND: The present article reports the updated survival outcome of the 200 patients enrolled in the Southern Italy Cooperative Oncology Group 9908 trial, which compared 12 weekly cycles of cisplatin-epirubicin-paclitaxel (PET) with 4 triweekly (once every 3 weeks) cycles of epirubicin-paclitaxel (ET) in patients with locally advanced breast cancer (LABC). METHODS: The effects of treatment, pathologically documented response (pathological response), pre- and post-treatment biomarkers on relapse-free survival (RFS), distant metastasis-free survival (DMFS), and overall survival (OS) are analysed. RESULTS: At a median follow-up of 74 (range 48-105 months) months, the 5-year RFS, DMFS, and OS were 64 % versus 53% (P = 0.11), 73% versus 55% (P = 0.04), and 82% versus 69% (P = 0.07) in PET and ET, respectively. At multivariate analysis, after adjusting treatment effect for pretreatment biomarkers, PET independently predicted better DMFS (P = 0.018) and OS (P = 0.03), whereas the impact on RFS was of borderline significance (0.057). PET treatment was significantly better than ET treatment only in high-grade or highly proliferating tumours. The better outcome in PET arm was the results of both the higher rate of patients with optimal pathological response and the lower rate of patients with biologically aggressive residual tumour. CONCLUSIONS: The PET weekly regimen significantly improves both DMFS and OS in LABC patients, compared with the triweekly ET combination. The therapeutic advantage is limited to patients with highly aggressive tumours.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/diagnosis , Breast Neoplasms/drug therapy , Carcinoma/diagnosis , Carcinoma/drug therapy , Adult , Aged , Algorithms , Breast Neoplasms/mortality , Breast Neoplasms/surgery , Carcinoma/mortality , Carcinoma/surgery , Cisplatin/administration & dosage , Combined Modality Therapy , Disease Progression , Drug Administration Schedule , Epirubicin/administration & dosage , Etoposide/administration & dosage , Female , Follow-Up Studies , Humans , Italy , Middle Aged , Paclitaxel/administration & dosage , Preoperative Care , Taxoids/administration & dosage
2.
Ann Oncol ; 20(7): 1185-92, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19218307

ABSTRACT

BACKGROUND: Findings from our previously published phase II study showed a high pathologic complete remission (pCR) rate in patients with triple-negative large operable breast cancer after the administration of eight cisplatin-epirubicin-paclitaxel (PET) weekly cycles. The safety and efficacy data of the initial population were updated, with inclusion of additional experience with the same therapy. METHODS: Patients with triple-negative large operable breast cancer (T2-T3 N0-1; T > 3 cm) received eight preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2, paclitaxel (Taxol) 120 mg/m2, with granulocyte colony-stimulating factor (5 microg/kg days 3-5) support. RESULTS: Overall 74 consecutive patients (T2/T3 = 35/39; N0/N+ = 26/48) were treated, from May 1999 to May 2008. At pathological assessment, 46 women (62%; 95% confidence interval 50-73) showed pCR in both breast and axilla. At a 41-month median follow-up (range 3-119), 13 events (nine distant metastases) had occurred, 5-year projected disease-free survival (DFS) and distant disease-free survival being 76% and 84%, respectively. Five-year DFS was 90% and 56% in pCRs and non-pCRs, respectively. Severe neutropenia and anemia occurred in 23 (31%) and eight (10.8%) patients, respectively. Severe non-hematological toxicity was recorded in <20% of patients. Peripheral neuropathy was quite frequent but never severe. CONCLUSIONS: Eight weekly PET cycles are a highly effective primary treatment in women with triple-negative large operable breast cancer. This approach results in a very promising long-term DFS in this poor prognosis population. This triplet regimen is worthy of evaluation in phase III trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Granulocyte Colony-Stimulating Factor/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/pathology , Cisplatin/administration & dosage , Disease-Free Survival , Drug Administration Schedule , Epirubicin/administration & dosage , Female , Follow-Up Studies , Humans , Middle Aged , Neoplasm Metastasis , Paclitaxel/administration & dosage , Preoperative Care , Treatment Outcome
3.
Nucleic Acids Res ; 36(4): 1163-75, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18158302

ABSTRACT

Ribonuclease III (RNaseIII) is responsible for processing and maturation of RNA precursors into functional rRNA, mRNA and other small RNA. In contrast to bacterial and yeast cells, higher eukaryotes contain at least three classes of RNaseIII, including class IV or dicer-like proteins. Here, we describe the functional characterization of AtRTL2, an Arabidopsis thaliana RNaseIII-like protein that belongs to a small family of genes distinct from the dicer family. We demonstrate that AtRTL2 is required for 3'external transcribed spacer (ETS) cleavage of the pre-rRNA in vivo. AtRTL2 localizes in the nucleus and cytoplasm, a nuclear export signal (NES) in the N-terminal sequence probably controlling AtRTL2 cellular localization. The modeled 3D structure of the RNaseIII domain of AtRTL2 is similar to the bacterial RNaseIII domain, suggesting a comparable catalytic mechanism. However, unlike bacterial RNaseIII, the AtRTL2 protein forms a highly salt-resistant homodimer that is only disrupted on treatment with DTT. These data indicate that AtRTL2 may use a dimeric mechanism to cleave double-stranded RNA, but unlike bacterial or yeast RNase III proteins, AtRTL2 forms homodimers through formation of disulfide bonds, suggesting that redox conditions may operate to regulate the activity of RNaseIII.


Subject(s)
Arabidopsis Proteins/chemistry , Arabidopsis/enzymology , Endoribonucleases/chemistry , RNA Precursors/metabolism , RNA, Ribosomal/metabolism , Ribonuclease III/chemistry , Amino Acid Sequence , Arabidopsis/embryology , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Catalytic Domain , Cell Nucleus/enzymology , Cytoplasm/enzymology , DNA, Ribosomal Spacer , Dimerization , Endoribonucleases/genetics , Endoribonucleases/metabolism , Models, Molecular , Molecular Sequence Data , Mutation , Nuclear Export Signals , RNA-Binding Proteins/chemistry , Ribonuclease III/genetics , Ribonuclease III/metabolism , Seeds/growth & development
4.
Ann Oncol ; 18(2): 324-30, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17071935

ABSTRACT

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles. RESULTS: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens. CONCLUSIONS: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Large Cell/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Squamous Cell/drug therapy , Lung Neoplasms/drug therapy , Adenocarcinoma/secondary , Adult , Aged , Carcinoma, Large Cell/secondary , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/secondary , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Female , Humans , Italy , Lung Neoplasms/pathology , Male , Middle Aged , Paclitaxel/administration & dosage , Prognosis , Survival Rate , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , Vinorelbine , Gemcitabine
5.
Br J Cancer ; 95(8): 1005-12, 2006 Oct 23.
Article in English | MEDLINE | ID: mdl-17047649

ABSTRACT

The present study aimed at evaluating whether a weekly cisplatin, epirubicin, and paclitaxel (PET) regimen could increase the pathological complete response (pCR) rate in comparison with a tri-weekly epirubicin and paclitaxel administration in locally advanced breast cancer (LABC) patients. Patients with stage IIIB disease were randomised to receive either 12 weekly cycles of cisplatin 30 mg m(-2), epirubicin 50 mg m(-2), and paclitaxel 120 mg m(-2) (PET) plus granulocyte-colony stimulating factor support, or four cycles of epirubicin 90 mg m(-2)+paclitaxel 175 mg m(-2) (ET) every 3 weeks. Overall, 200 patients (PET/ET=100/100) were included in this study. A pCR in both breast and axilla occurred in 16 (16%) PET patients and in six (6%) ET patients (P=0.02). The higher activity of PET was evident only in ER negative (27.5 vs 5.4%; P=0.026), and in HER/neu positive (31 vs 5%; P=0.037) tumours. The two arms yielded similar pCR rate in ER positive (PET/ET=7.5/7.1%) and HER/neu negative (PET/ET=10/6%) patients. At a 39 months median follow-up, 70 patients showed a progression or relapses (PET, 32 vs ET, 38). Anaemia, mucositis, peripheral neuropathy, and gastrointestinal toxicity were substantially more frequent in the PET arm. The PET weekly regimen is superior to ET in terms of pCR rate in LABC patients with ER negative and/or HER2 positive tumours Mature data in terms of disease-free and overall survival are needed to ascertain whether this approach could improve the prognosis of these subsets of LABC patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Anemia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Diarrhea/chemically induced , Drug Administration Schedule , Epirubicin/administration & dosage , Epirubicin/adverse effects , Fatigue/chemically induced , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Granulocyte Colony-Stimulating Factor/adverse effects , Humans , Kaplan-Meier Estimate , Middle Aged , Neutropenia/chemically induced , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Patient Compliance/statistics & numerical data , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Treatment Outcome
6.
Br J Cancer ; 94(12): 1809-15, 2006 Jun 19.
Article in English | MEDLINE | ID: mdl-16736001

ABSTRACT

Oxaliplatin (OXA), raltitrexed (RTX), 5-fluorouracil (FU) and folinic acid (FA) have shown activity in metastatic colorectal cancer, radioenhancing effect and synergism when combined. We evaluated a chemotherapy (CT) combination of OXA, RTX and FU/FA during preoperative radiotherapy (RT) in locally advanced rectal cancer (LARC) patients. Fifty-one patients with LARC at high risk of recurrence (T4, N+ or T3N0 < or =5 cm from anal verge and/or circumferential resection margin < or =5 mm) received three biweekly courses of CT during pelvic RT (45 Gy). Surgery was planned 8 weeks after CT-RT. Recommended doses (RDs) determined during phase I were utilised in the subsequent phase II trial, where the rate of tumour regression grade (TRG) 1 or 2 was the main end point. No toxic deaths occurred, and severe toxicity was easily managed. In phase II, RDs delivered in 31 patients were OXA 100 mg m(-2) and RTX 2.5 mg m(-2) on day 1, and FU 900 mg m(-2) and LFA 250 mg m(-2) on day 2. Main severe toxicities by patients were grade 4 neutropenia (23%) and grade 3 diarrhoea (19%). In 71% (95% confidence limits, 52-86%) of patients, TRG1 (13) or TRG2 (9) was obtained. All patients are alive and recurrence-free after a median follow-up of 29 months. Combination of OXA, RTX and FU/FA with pelvic RT has an acceptable toxicity and a high clinical activity in LARC and should be studied further in patients at high risk of recurrence.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/therapy , Neoadjuvant Therapy , Preoperative Care , Adult , Aged , Digestive System Surgical Procedures , Dose-Response Relationship, Drug , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Quinazolines/administration & dosage , Quinazolines/adverse effects , Thiophenes/administration & dosage , Thiophenes/adverse effects
7.
Ann Oncol ; 16(8): 1268-75, 2005 Aug.
Article in English | MEDLINE | ID: mdl-15937055

ABSTRACT

PURPOSE: The present study aimed to define the antitumor activity of eight cisplatin-epirubicin-paclitaxel (PET) weekly cycles with granulocyte colony-stimulating factor (G-CSF) support in patients with large operable breast cancer. METHODS: Operable breast cancer (T2-3 N0-1; T >3 cm) patients received eight preoperative weekly cycles of cisplatin 30 mg/m2, epirubicin 50 mg/m2 and paclitaxel 120 mg/m2, with G-CSF (5 microg/kg, days 3-5) support. RESULTS: Sixty-three patients (T2/T3=30/33; N0/N+=8/55) were enrolled. Thirty-one clinical complete (49%) and 30 partial (48%) responses were recorded, giving a 97% response rate (95% confidence interval 89% to 100%). Breast-sparing surgery was performed in 32/63 (51%) patients. At pathological assessment, 28 patients (45%) showed absence of invasive residual disease in breast and 34 (55%) had negative axilla. In 20 women (32%) both breast and axilla were found to be disease-free. At a 23-month median follow-up (range 4-63), only eight relapses and two deaths had occurred, with the 4-year projected relapse-free and overall survival being 59% and 95%, respectively. Grade 3-4 neutropenia and anemia occurred in 24% and 5% of patients, respectively. Emesis, diarrhea and mucositis were the main non-hematological toxicities; however, only nine (14%) patients experienced one or more episodes of severe non-hematological toxicity. Peripheral neuropathy was frequent, but never severe. CONCLUSIONS: A 2-month weekly treatment with PET represents a well tolerated and highly effective approach in large operable breast cancer patients. In spite of the short duration of chemotherapy, one-third of patients achieved a complete eradication of the tumor in both breast and axilla.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/surgery , Cisplatin/administration & dosage , Epirubicin/administration & dosage , Feasibility Studies , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Middle Aged , Paclitaxel/administration & dosage , Preoperative Care , Survival Rate
8.
Cancer Chemother Pharmacol ; 56(5): 481-6, 2005 Nov.
Article in English | MEDLINE | ID: mdl-15902461

ABSTRACT

Oxaliplatin 100 mg/m(2) iv on day 1, and capecitabine 1,000 mg/m(2) orally bid from day 1 (evening) to day 11 (morning) were administered every 2 weeks (OXXEL regimen) to 38 patients as first-line treatment for metastatic colorectal carcinoma. A total of 318 cycles were administered, with a median of 8 (range, 4-12) cycles per patient. Response rate (RR) was 45% (95% confidence interval (CI), 29%-62%), with 7 complete responses and 10 partial responses; furthermore, 12 patients showed a stable disease, so that a disease control was achieved in 29 (76%) patients. RR was greater among patients with performance status 0 (52%), without weight loss (52%), younger than 65 years (50%), and previously unexposed to adjuvant chemotherapy (48%), while no correlation was found with the actually delivered oxaliplatin dose intensity. Overall, haematological side effects were negligible, with no case of grade 4 toxicity, and only one patient suffering from an episode of grade 3 neutropenic fever. Severe anaemia occurred in 4 (11%) patients, and grade 3 neuropathy affected 9 (24%) patients. Median progression-free survival was 7.9 (95% CI, 6.2-9.6) months, and median overall survival has not been reached yet. In conclusion, the OXXEL regimen resulted safe and active, and it deserves further evaluation in metastatic colorectal cancer patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/drug therapy , Colorectal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Capecitabine , Carcinoma/pathology , Carcinoma/secondary , Colorectal Neoplasms/pathology , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Female , Fluorouracil/analogs & derivatives , Humans , Italy , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Lung Neoplasms/drug therapy , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary
9.
Ann Oncol ; 16(6): 878-86, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15837702

ABSTRACT

PURPOSE: The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma. PATIENTS AND METHODS: Patients with measurable metastatic colorectal carcinoma were randomly allocated to receive: IRI 200 mg/m(2) on day 1, l-FA 250 mg/m(2) intravenously plus 5-FU 850 mg/m(2) on day 2 (IRIFAFU); or OXA 100 mg/m(2) on day 1, l-FA 250 mg/m(2) plus 5-FU 1050 mg/m(2) on day 2 [OXAFAFU high dose (hd)]. Cycles were given every 2 weeks. After a planned interim analysis, OXA was reduced to 85 mg/m(2) and 5-FU to 850 mg/m(2) [OXAFAFU low dose (ld)]. RESULTS: Two hundred and seventy-four patients (IRIFAFU, 135; OXAFAFUhd, 71; OXAFAFUld, 68) were treated. Forty-two confirmed responses were achieved with IRIFAFU, 29 with OXAFAFUhd and 32 with OXAFAFUld. The response rate with OXAFAFU [44%; 95% confidence interval (CI) 35% to 52%] was significantly higher (P=0.029) than that of IRIFAFU (31%; 95% CI 23% to 40%). Occurrence of grade > or =3 neutropenia with OXAFAFUld was similar to that for IRIFAFU (29% versus 31%), while severe diarrhoea was significantly lower (12% versus 24%). Median failure-free survival (7 versus 5.8 months; P=0.046) and overall survival of patients (18.9 versus 15.6 months; P=0.032) were significantly prolonged with OXAFAFU. CONCLUSIONS: OXAFAFU was more active and less toxic than IRIFAFU, and it should be preferred in the first-line treatment of advanced colorectal cancer patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Colorectal Neoplasms/mortality , Female , Fluorouracil/administration & dosage , Humans , Leucovorin/administration & dosage , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin
10.
Oncol Rep ; 13(2): 283-7, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15643512

ABSTRACT

The purpose of the study was to evaluate the antitumor activity and the safety of paclitaxel combined with gemcitabine and cisplatin in patients affected by advanced transitional cell carcinoma of the urothelium (TCC). Eighty-five patients affected by advanced TCC and measurable disease were randomized to receive either paclitaxel at dosage of 70 mg/m2, gemcitabine 1000 mg/m2 and cisplatin 35 mg/m2 on days 1 and 8 every 3 weeks (GCP) or gemcitabine 1000 mg/m2 on days 1, 8, 15 and cisplatin 70 mg/m2 on day 2 every 4 weeks (GC). All enrolled patients were considered evaluable for response and toxicity (intention to treat). The observed response rate was 43% for GCP and 44% for GC combination, respectively. Median time to treatment failure was 32 weeks for GCP and 26 weeks for GC and overall survival 61 vs 49 weeks, respectively (p-value not significant). Grade 3-4 neutropenia was observed in 49% of patients treated with GCP vs 35% of those treated with GC (P=0.05) and grade 3-4 thrombocytopenia was observed in 36% of GCP treated patients as compared to 21% of those treated with GC (P=0.01). Seven patients over 70 years old or with poor PS were removed from the study: 6 patients from GCP group (2 toxic deaths, 2 grade 4 myelotoxicity and 2 grade 3 asthenia) and 1 from GC group was lost to follow-up after the first cycle. The combination of paclitaxel, gemcitabine and cisplatin is effective in the treatment of TCC. However, the addition of paclitaxel to the combination of gemcitabine plus cisplatin seems to increase toxicity, therefore it seems not suitable for poor PS patients and those over 70 years old. Larger and more powered studies are needed to exactly define the role of paclitaxel in this combination.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Deoxycytidine/analogs & derivatives , Kidney Neoplasms/drug therapy , Urinary Bladder Neoplasms/drug therapy , Urothelium , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Female , Humans , Male , Middle Aged , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Time Factors , Gemcitabine
11.
Br J Cancer ; 91(3): 489-97, 2004 Aug 02.
Article in English | MEDLINE | ID: mdl-15266334

ABSTRACT

The aim of this study was to assess whether a combination of gemcitabine (GEM) with either paclitaxel (PTX) or vinorelbine (VNR) could be more effective than GEM or PTX alone in elderly or unfit advanced non-small-cell lung cancer (NSCLC) patients. A total of 264 NSCLC patients aged >70 years with ECOG performance status (PS)< or =2, or younger with PS=2, were randomly treated with: GEM 1200 mg m(-2) on days 1, 8 and 15 every 28 days; PTX 100 mg m(-2) on days 1, 8 and 15 every 28 days; GEM 1000 mg m(-2) plus PTX 80 mg m(-2) (GT) on days 1 and 8 every 21 days; GEM 1000 mg m(-2) plus VNR 25 mg m(-2) (GV) on days 1 and 8 every 21 days. In all arms, an intra-patients dose escalation was applied over the first three courses, provided that no toxicity of WHO grade > or =2 had previously occurred. At present time, 217 (82%) patients had died. The median (months) and 1-year survival probability were 5.1 and 29% for GEM, 6.4 and 25% for PTX, 9.2 and 44% for GT, and 9.7 and 32% for GV. Multivariate analysis showed that PS< or =1 (hazard ratio (HR)=0.67; 95% CI 0.51-0.90), and doublet treatments (HR=0.76; 95% CI 0.59-0.99) were significantly associated with longer survival. Doublets produced no more toxicity than single agents. GT should be considered a reference regimen for elderly NSCLC patients with PS< or =1.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Lung Neoplasms/drug therapy , Paclitaxel/therapeutic use , Vinblastine/analogs & derivatives , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Deoxycytidine/administration & dosage , Female , Health Status , Humans , Infusions, Intravenous , Lung Neoplasms/pathology , Male , Middle Aged , Paclitaxel/administration & dosage , Survival Analysis , Vinblastine/administration & dosage , Vinorelbine , Gemcitabine
12.
Br J Cancer ; 89(6): 992-6, 2003 Sep 15.
Article in English | MEDLINE | ID: mdl-12966414

ABSTRACT

The aim of this study was to assess the safety and efficacy of biweekly irinotecan plus leucovorin-modulated 5-fluorouracil i.v. bolus in metastatic colorectal carcinoma according to the age of patients. For this purpose, we have analysed 108 patients randomly allocated to receive irinotecan 200 mg m(-2) i.v. (1-h infusion) on day 1, and L-leucovorin 250 mg m(-2) i.v. (1-h infusion) plus 5-fluorouracil 850 mg m(-2) i.v. bolus on day 2 every 2 weeks (IRIFAFU) in our previous SICOG 9801 trial. According to age, patients were retrospectively divided into three groups: younger (/=70 years, n=17). Apart from gender, pretreatment characteristics were well balanced across the three groups. WHO grade >/=3 neutropenia and diarrhoea affected on the whole 46 and 16 patients, respectively, without any significant difference according to age-grouping. Patients aged

Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Adenocarcinoma/secondary , Adult , Aged , Camptothecin/administration & dosage , Colorectal Neoplasms/pathology , Disease-Free Survival , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Irinotecan , Leucovorin/administration & dosage , Male , Middle Aged , Retrospective Studies , Survival Rate , Treatment Outcome
13.
Ann Oncol ; 14 Suppl 2: ii7-12, 2003.
Article in English | MEDLINE | ID: mdl-12810451

ABSTRACT

The chemotherapy of metastatic colorectal cancer (CRC) has undergone a succession of refinements. Through the biochemical modulation of 5-fluorouracil (5-FU) with folinic acid (FA), the use of infusional rather than bolus regimens and the combination of 5-FU/FA with other active agents (notably irinotecan), first-line response rates (RRs) of 40% can be achieved, with patients surviving up to 17 months. Significant benefits on survival are also seen with second-line chemotherapy. The question of how best to sequence combination chemotherapy was addressed in a recent trial in which patients were randomized to receive either an irinotecan-based combination with 5-FU/FA (FOLFIRI) followed by an oxaliplatin-based combination (FOLFOX), or the two regimens in the reverse order. In both arms, RRs were greater than 50% and median survival exceeded 20 months. The primary end point was time to progression after two lines of treatment, and this was not significantly different. However, the sequence FOLFIRI followed by FOLFOX appears preferable because of the better tolerability of FOLFIRI in first-line use. Use of the sequence FOLFIRI/FOLFOX is also supported by the greater chance of a second-line response with FOLFOX. Concern has been expressed about the safety of irinotecan combined with bolus 5-FU/FA. Infusional regimens have a better risk/benefit ratio than bolus regimens. However, the adverse event profile with both approaches is manageable, and irinotecan plus 5-FU/FA can be considered one standard of care in metastatic CRC.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Camptothecin/administration & dosage , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Fluorouracil/administration & dosage , Humans , Irinotecan , Leucovorin/administration & dosage , Organoplatinum Compounds , Survival Rate , Treatment Outcome
14.
Ann Oncol ; 13(12): 1874-81, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12453855

ABSTRACT

BACKGROUND: Oxaliplatin (OXA) and irinotecan (IRI) are active drugs in first-line as well as second-line treatment of advanced colorectal cancer patients, their toxicity profiles are not overlapping, and both drugs have shown synergism with folinic acid-modulated 5-fluorouracil (5-FU). We planned this phase I study to define the dose-limiting toxicities (DLTs), the maximum tolerated doses (MTDs), and the recommended doses (RDs) for a triplet regimen including OXA plus IRI on day 1, and 6S-folinic acid (LFA) plus 5-FU on day 2, every 2 weeks. PATIENTS AND METHODS: At least three patients had to be treated at each dose level, and the trial proceeded if no more than 33% of patients showed a DLT after the first cycle. Starting from OXA 85 mg/m(2) (over 2 h) and IRI 150 mg/m(2) (over 1 h), an alternated escalation was planned up to 110 mg/m(2) and 200 mg/m(2), respectively. Thereafter, a fixed dose of LFA, 250 mg/m(2) (as 2-h infusion), plus an escalating dose of 5-FU (from 650 to 800 mg/m(2) as an intravenous bolus) was added on day 2 to the previous dose level of OXA and IRI. RESULTS: Forty-six patients, all but four affected by advanced colorectal primaries, entered this study. The MTDs for OXA and IRI given on the same day were 110 and 200 mg/m(2): these doses caused a DLT in three of six patients. The previous dose level (110 and 175 mg/m(2), respectively) on day 1 was safely followed on day 2 by LFA plus 5-FU up to 800 mg/m(2). Indeed, only one of three patients treated at this last level had a DLT. This cohort was then expanded including a total of 14 patients, and on the whole series five cases of DLT occurred: WHO grade 4 neutropenia (two patients), grade 3 or 4 diarrhoea (three patients). Cumulative toxicity was analysed in 43 patients for a total of 347 cycles: grade 4 neutropenia was detected in 13 patients (30%); it was not dose-related, nor was it exacerbated by the addition of modulated 5-FU. Febrile neutropenia occurred in four patients. Grade 3 or 4 diarrhoea was suffered by nine (21%) and five (12%) patients, respectively. Two complete and nine partial responses were reported on 40 evaluable patients (six patients were disease-free at study entry), giving a response rate of 27.5% (95% confidence interval 15% to 44%); nine of 18 (50%) assessable patients of the two last cohorts treated with the triplet regimen achieved a complete response (two patients) or a partial response (seven patients). CONCLUSIONS: The RDs for this biweekly regimen were: OXA 110 mg/m(2) plus IRI 175 mg/m(2) on day 1, and LFA 250 mg/m(2) plus 5-FU 800 mg/m(2) on day 2. This regimen appeared active in pretreated gastrointestinal malignancies, and it is worthy of being evaluated in advanced colorectal carcinoma after failure of 5-FU-based adjuvant or palliative treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Maximum Tolerated Dose , Adolescent , Adult , Aged , Biopsy, Needle , Camptothecin/administration & dosage , Camptothecin/adverse effects , Colorectal Neoplasms/mortality , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/pathology , Humans , Infusions, Intravenous , Irinotecan , Leucovorin/administration & dosage , Male , Middle Aged , Neoplasm Staging , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Prognosis , Pyridines/administration & dosage , Pyridines/adverse effects , Survival Analysis , Treatment Outcome
15.
Ann Oncol ; 13(6): 866-73, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12123331

ABSTRACT

PURPOSE: The purpose of this study was to compare the activity and toxicity of the combination of irinotecan (IRI) plus folinic acid (FA)-modulated 5-fluorouracil (5-FU) i.v. bolus with a regimen of double modulation of 5-FU with methotrexate (MTX) and FA in patients with advanced colorectal carcinoma. PATIENTS AND METHODS: Two-hundred and thirty-four patients were enrolled: 118 patients received IRI 200 mg/m2 (90-min i.v. infusion) on day 1, followed by levo-FA 250 mg/m2 (2-h i.v. infusion) and 5-FU 850 mg/m2 (i.v. bolus) on day 2 (IRIFAFU), and 116 patients received MTX 750 mg/m2 (2-h i.v. infusion) on day 1, followed by levo-FA 250 mg/m2 (2-h i.v. infusion) and FU 800 mg/m2 (i.v. bolus) on day 2 (MTXFAFU). Both cycles were repeated every 2 weeks until progression or to a maximum of 16 cycles. Response rate (RR) was the main end point of the study; responses were assessed every four cycles and confirmed after 2 additional months of treatment. RESULTS: RR was significantly greater with IRIFAFU (36%) than with MTXFAFU (20%) (P <0.001). Multivariate analysis showed that IRIFAFU was significantly associated with a greater activity (P = 0.028). Median progression-free survival was longer with IRIFAFU than with MTXFAFU (7.2 months compared with 4.8 months; P = 0.048). Median survival time (MST) did not differ between the two arms (14.7 months compared with 14.8 months, respectively). Patients not receiving second-line chemotherapy, however, lived longer when treated in the first-line with IRIFAFU (MST 11.9 months compared with 6.4 months; P = 0.038). IRIFAFU caused a significantly greater occurrence of grade 3 or 4 neutropenia (40% compared with 9%; P = 0.001) and diarrhoea (13% compared with 4%; P = 0.024), but a significantly lower incidence of stomatitis (3% compared with 12%; P = 0.007), than the comparative regimen. CONCLUSIONS: IRIFAFU appeared comparable in terms of activity and toxicity with other weekly or biweekly bolus or infusional combination regimens. IRIFAFU, however, seems easier to administer, because it does not require infusional catheter or pump devices, and it is less expensive. It may represent a new option for treating advanced colorectal carcinoma.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Adenocarcinoma/mortality , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Biopsy, Needle , Camptothecin/administration & dosage , Camptothecin/adverse effects , Colorectal Neoplasms/mortality , Disease-Free Survival , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Irinotecan , Italy , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Neoplasm Staging , Prognosis , Remission Induction , Survival Analysis , Treatment Outcome
16.
Br J Cancer ; 86(12): 1871-5, 2002 Jun 17.
Article in English | MEDLINE | ID: mdl-12085178

ABSTRACT

The aim of the present study was to define the activity and tolerability of a triplet regimen including oxaliplatin 130 mg x m(-2) (2 h i.v. infusion) and raltitrexed 3.0 mg x m(-2) (15 min i.v. infusion) given on day 1, followed by levo-folinic acid 250 mg x m(-2) (2 h i.v. infusion) and 5-fluorouracil 1050 mg x m(-2) i.v. bolus on day 2, every 2 weeks, in pretreated colorectal cancer patients. From April 1999 to December 2000, 50 patients were enrolled: 26 were males and 24 females, their median age was 63 (range, 43-79) years; ECOG performance status was 0 in 26 patients, > or =1 in 24 patients; 26 patients had received previous adjuvant chemotherapy, 40 patients had been exposed to one or two lines of palliative chemotherapy (including irinotecan in 31 cases); 18 patients were considered chemo-refractory. A total of 288 cycles were administered, with a median number of 6 (range 1-12) courses per patient. A complete response was obtained in three patients, and a partial response in nine patients, giving a major response rate of 24% (95% confidence interval, 13-38%), while 15 further patients showed a stable disease, for an overall control of tumour growth in 60% of patients. Three complete responses and three partial responses were obtained in patients pretreated with irinotecan (response rate, 19%); among refractory patients, three achieved partial responses (response rate, 13%). After a median follow-up of 18 (range, 10-30) months, 40 patients showed a progression of disease: the growth modulation index ranged between 0.2 and 2.5: it was > or =1.33 (showing a significant delay of tumour growth) in 16 (40%) patients. Actuarial median progression-free survival time was 7.6 months, and median survival time was 13.6 months: estimated probability of survival was 55% at 1 year. Main severe toxicity was neutropenia: World Health Organisation grade 4 affected 32% of patients; non-haematological toxicity was mild: World Health Organisation grade 3 diarrhoea was complained of by 8%, and grade 3 stomatitis by 4% of patients; neurotoxicity (according to Lévi scale) was scored as grade 3 in 8% of patients. In conclusion, this regimen was manageable and active as salvage treatment of advanced colorectal cancer patients; it showed incomplete cross-resistance with irinotecan-based treatments, and proved to delay the progression of disease in a relevant proportion of treated patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Colorectal Neoplasms/pathology , Disease Progression , Drug Resistance, Neoplasm , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Infusions, Intravenous , Irinotecan , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Quinazolines/administration & dosage , Quinazolines/adverse effects , Salvage Therapy , Thiophenes/administration & dosage , Thiophenes/adverse effects , Treatment Outcome
17.
Lung Cancer ; 34 Suppl 4: S65-9, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11742706

ABSTRACT

OBJECTIVE: This phase III study was aimed at evaluating whether the addition of gemcitabine (G) to vinorelbine (V) could improve the survival and quality of life (QoL) of elderly patients with advanced NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC, aged >or=70 years, were randomly allocated to receive V 30 mg/m(2) on days 1 and 8 every 3 weeks or G 1200 mg/m(2) plus V 30 mg/m(2) on days 1 and 8 every 3 weeks. Survival was the main end point of the study. The estimated sample size was 120 patients per arm, but an interim analysis of survival was planned on the first 60 patients per arm. RESULTS: In May 1999, an interim analysis was performed with the survival data of the first 120 eligible patients (V(arm)=60, G+V(arm)=60). Forty-nine patients had stage IIIB disease and 71 patients stage IV disease, median potential follow-up of 14 months (range; 3-22), 93 patients had died (G+V(arm)=41, V(arm)=52). Median survival time (MST) was 29 weeks and projected 1-year survival was 30% in the G+V(arm); these values were 18 weeks and 13% in the V(arm). At multivariate Cox analysis, the risk of death in the G+V(arm) compared with V(arm) was 0.48 (95% C1=0.29-0.79; P<0.01). Combination therapy was also associated with a clear delay in symptom and QoL deterioration. The ORR was 22 and 15% in the G+V and V(arms), respectively. Toxicity was not irrelevant in both arms. CONCLUSIONS: G+V treatment is associated with a significantly better survival than V alone in elderly NSCLC patients. The magnitude of the difference justifies the early closure of the study. The G+V regimen is now the SICOG reference regimen in this type of patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Lung Neoplasms/drug therapy , Vinblastine/analogs & derivatives , Aged , Aged, 80 and over , Antineoplastic Agents, Phytogenic/therapeutic use , Deoxycytidine/administration & dosage , Female , Humans , Male , Quality of Life , Survival Analysis , Vinblastine/administration & dosage , Vinblastine/therapeutic use , Vinorelbine , Gemcitabine
18.
Semin Oncol ; 28(3 Suppl 10): 50-6, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11510034

ABSTRACT

We sought to define the recommended dose of cyclophosphamide (CTX) for subsequent phase II assessment when combined with fixed doses of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) and 5-fluorouracil/folinic acid in metastatic breast cancer patients previously treated with anthracyclines and taxanes. Patients age 70 or less, with an Eastern Cooperative Oncology Group performance status 0 to 2, were enrolled. Patients received gemcitabine 1,000 mg/m(2), 5-fluorouracil 425 mg/m(2), folinic acid 100 mg/m(2), and escalating doses of CTX (in 100-mg/m(2) increments), starting at 500 mg/m(2), on days 1 and 8 every 3 weeks. Since March 1999, 46 patients, with a median age of 51 years (range, 38 to 74 years), entered the trial in seven cohorts. Cyclophosphamide dose escalation was stopped at 600 mg/m(2) when three of six patients experienced dose-limiting toxicity (one each with grade 3 thrombocytopenia, grade 3 neutropenia, and persistent grade 2 neutropenia), and then continued with granulocyte colony-stimulating factor support. The CTX dose of 800 mg/m(2) was proven safe and was chosen for phase II study. Two complete and 15 partial responses provided an overall response rate of 37% (95% confidence interval, 23% to 51%). Gemcitabine/CTX/5-fluorouracil/folinic acid is well tolerated by metastatic breast cancer patients pretreated with anthracyclines/taxanes, up to a CTX dose of 800 mg/m(2). The phase II study is ongoing. Semin Oncol 28 (suppl 10):50-56.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Antibiotics, Antineoplastic , Breast Neoplasms/pathology , Cyclophosphamide/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Resistance, Neoplasm , Fluorouracil/administration & dosage , Humans , Leucovorin/therapeutic use , Middle Aged , Neoplasm Metastasis , Paclitaxel , Gemcitabine
19.
Anticancer Drugs ; 12(6): 489-97, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11459994

ABSTRACT

Preclinical evidence of a schedule-dependent synergism between raltitrexed and 5-fluorouracil (5-FU) has prompted clinical studies of this combination. We review the main preclinical and clinical results of raltitrexed/5-FU-based combination chemotherapy regimens in anticancer therapy. Promising results include: response rates of 25 and 23% with combinations of raltitrexed/5-FU/levofolinic acid (LFA) as first-line treatment and oxaliplatin/raltitrexed/5-FU/LFA as second-line treatment of metastatic colorectal cancer, respectively; and a 67% response rate in a phase I study of cisplatin/raltitrexed/5-FU/LFA as first-line treatment of advanced head and neck cancer, including a 100% response rate at the recommended dose. These combinations were well tolerated, with neutropenia as the main dose-limiting toxicity, allowing the drugs to be combined at the doses used in monotherapy. These results suggest a role for raltitrexed within combination regimens in colorectal cancer therapy, as well as other tumors such as head and neck cancer. A further potential application of raltitrexed in combination therapies is within multidisciplinary chemo-radiotherapy strategies, mainly in rectal cancer. Phase II studies are planned/ongoing to investigate these interesting possibilities.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil/administration & dosage , Leucovorin/administration & dosage , Neoplasms/drug therapy , Quinazolines/administration & dosage , Thiophenes/administration & dosage , Clinical Trials as Topic , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Head and Neck Neoplasms/drug therapy , Humans , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy
20.
Br J Cancer ; 84(9): 1166-71, 2001 May 04.
Article in English | MEDLINE | ID: mdl-11336465

ABSTRACT

The present study was aimed at defining the antitumour activity of the cisplatin-paclitaxel-topotecan (CPT) weekly administration with G-CSF support in chemo-naive SCLC patients with extensive disease (ED-SCLC). Chemonaive ED-SCLC patients received cisplatin 40 mg/m(2), paclitaxel 85 mg/m(2), and topotecan 2.25 mg/m(2)weekly, with G-CSF (5 microg/kg days 3-5) support, for a maximum of 12 weeks. 37 patients were treated, for a total of 348 cycles delivered. 8 complete responses (22%) and 22 partial responses (59%) were recorded, giving an 81% [95% CI = 65-92%] ORR. At a 13-month (range, 4-26) median follow-up, median progression-free and overall survival were 8 months and 12.5 months, with 1-year and 2-year projected survivals of 55% and 21%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 3 patients, respectively. Only one case of neutropenic sepsis was recorded, while haemorrhagic thrombocytopenia was never observed. Diarrhoea, paraesthesias and fatigue were the main nonhaematologic toxicities being severe in 6, 2 and 10 patients, respectively. The weekly CPT combination with G-CSF support represents a well tolerated therapeutic approach in chemo-naive ED-SCLC patients. The activity rate seems at least similar to that achievable with the standard front-line approaches.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Small Cell/pathology , Cisplatin/administration & dosage , Disease-Free Survival , Drug Administration Schedule , Female , Granulocyte Colony-Stimulating Factor/administration & dosage , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Neutropenia/chemically induced , Paclitaxel/administration & dosage , Taxoids , Thrombocytopenia/chemically induced , Topotecan/administration & dosage
SELECTION OF CITATIONS
SEARCH DETAIL
...