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2.
Ann Oncol ; 23(1): 135-141, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21531784

ABSTRACT

BACKGROUND: Previous studies investigating the prognostic role of mucinous histology of colorectal cancer produced conflicting results. This retrospective analysis was carried out in order to explore whether mucinous adenocarcinoma (MC) is associated with a comparatively worse prognosis than that of nonmucinous adenocarcinoma (NMC) for patients undergoing curative resection for stage II and III colon cancer. PATIENTS AND METHODS: This study involved 1025 unselected patients who underwent curative surgery for sporadic colon cancer and follow-up procedures at six different oncology departments. RESULTS: MCs accounted for 17.4% (n=178) of tumours. Patients with MC had 5- and 8-year overall survival rates of 78.6% and 68.8%, respectively, compared with 72.3% and 63.8%, respectively, for patients with nonmucinous tumours. Multivariate analysis using the Cox proportional hazards model showed that the clinically significant prognostic factors were stage of disease and adjuvant chemotherapy. No statistically significant interaction between mucinous histology and adjuvant chemotherapy was found. CONCLUSIONS: For patients with stage II and III colon cancer who underwent curative surgery, mucinous histology has no significant correlation with prognosis compared with NMC. This retrospective analysis suggests a comparable benefit from adjuvant chemotherapy for MC compared with NMC.


Subject(s)
Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/pathology , Colonic Neoplasms/mortality , Colonic Neoplasms/pathology , Adenocarcinoma, Mucinous/surgery , Adult , Aged , Aged, 80 and over , Chemotherapy, Adjuvant , Colonic Neoplasms/surgery , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Retrospective Studies
3.
World J Oncol ; 2(5): 245-251, 2011 Oct.
Article in English | MEDLINE | ID: mdl-29147255

ABSTRACT

BACKGROUND: Schedules with anthracyclines and taxanes are one of the best options for primary chemotherapy. The addition of trastuzumab showed an impressive percentage of pathological complete responses in Buzdar trial (66.7%). Recently, nonpegylated liposome-encapsulated doxorubicin (NLD) has been widely used in advanced breast cancer with high response rates (98.1 % in Cortes study). The aims of our study were to assess pathological responses and toxicity of NLD plus paclitaxel (and trastuzumab in patients with HER2 overexpression). METHODS: Thirty patients entered the study: 9 locally advanced and 21 operable. Median age was 58.5 years (range: 31-73). 23 patients without HER2 overexpression (or FISH not amplified) were treated with NLD 50 mg/m2 every three weeks for 3 courses and weekly paclitaxel 80 mg/m2 for 8 courses. 7 patients with HER2 overexpression or FISH amplified were treated with the same schedules plus trastuzumab (Herceptin) 4 mg/kg for the first administration and 2 mg/kg for the following 7 weekly administrations. RESULTS: Pathological complete response (pCR) was documented in 1 patient (treated with trastuzumab); no residual tumor (infiltrating or "in situ") on breast was documented in other 2 patients. Objective clinical responses were documented in 22 patients (73.3%): 8 complete, 10 partial and 4 "minimal" responses. 7 patients have shown stable and 1 progressive disease. Clinical response in patients with HER2 overexpression treated with trastuzumab was 100% (4 complete and 3 partial responses). Conservative surgery was performed in 8 (38%) and mastectomy in 13 (62%) out of 21 operable patients; however, 7 out of 14 responding patients with operable disease underwent quadrantectomy (50%). Main toxicity was neutropenia: febrile in 2 patients (7%) and gr. 3-4 in 13 (43%). Other grade 3 toxicities were as follows: vomiting in 1 patient, asthenia in 1 patient, joint symptom in 1 patient. 3 patients were withdrawn from the study. No episodes of left ventricular ejection fraction (LVEF) < 50% were recorded (with a median reduction of 8%). CONCLUSIONS: A "short course" of paclitaxel and NLD is active in terms of clinical response and conservative surgery for patients with potentially operable and locally advanced breast cancer; toxicity was manageable. High activity of the combination with trastuzumab has been confirmed. However, with this "short course" schedule, the result in term of clinical responses didn't turn into complete pathological responses.

4.
Br J Cancer ; 100(6): 881-7, 2009 Mar 24.
Article in English | MEDLINE | ID: mdl-19259089

ABSTRACT

The objective of this study was to investigate the efficacy of first-line chemotherapy containing irinotecan and/or oxaliplatin in patients with advanced mucinous colorectal cancer. Prognostic factors associated with response rate and survival were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The population included 255 patients, of whom 49 (19%) had mucinous and 206 (81%) had non-mucinous colorectal cancer. The overall response rates for mucinous and non-mucinous tumours were 18.4 (95% CI, 7.5-29.2%) and 49% (95% CI, 42.2-55.8%), respectively (P=0.0002). After a median follow-up of 45 months, median overall survival for the mucinous patients was 14.0 months compared with 23.4 months for the non-mucinous group (hazard ratio (HR), 1.74; CI 95%, 1.27-3.31; P=0.0034). After adjustment for significant features by multivariate Cox regression analysis, mucinous histology was associated with poor overall survival (HR, 1.593, 95% CI, 1.05-2.40; P=0.0267), together with performance status ECOG 2, number of metastatic sites > or =2, and peritoneal metastases. This retrospective analysis shows that patients with mucinous colorectal cancer have poor responsiveness to oxaliplatin/irinotecan-based first-line combination chemotherapy and an unfavourable prognosis compared with non-mucinous colorectal cancer patients.


Subject(s)
Adenocarcinoma, Mucinous/drug therapy , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Camptothecin/analogs & derivatives , Colorectal Neoplasms/drug therapy , Organoplatinum Compounds/administration & dosage , Adenocarcinoma, Mucinous/genetics , Adenocarcinoma, Mucinous/mortality , Adenocarcinoma, Mucinous/pathology , Adult , Aged , Aged, 80 and over , Camptothecin/administration & dosage , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Female , Humans , Irinotecan , Male , Microsatellite Instability , Middle Aged , Oxaliplatin , Retrospective Studies
5.
Pharmacogenomics J ; 9(1): 78-84, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19104506

ABSTRACT

The interleukin-1 receptor antagonist (IL-1RA) cytokine is thought to counteract tumor angiogenesis/metastasis. Two single nucleotide polymorphisms in the IL-1RA gene (rs4251961 T/C and rs579543 C/T) influence IL-1RA circulating levels with highest production in carriers of the homozygous rs4251961 T/T and rs579543 T/T genotypes. A total of 180 patients with metastatic colorectal cancer were categorized as high IL-1RA producers if they were carriers of at least one of the rs4251961 T/T or rs579543 T/T genotypes (T/T carriers). Median survival times were 35.8 months (95% confidence interval: 29.7-43.7 months) and 28.6 months (95% confidence interval: 25.6-30 months) in 56 T/T carriers and in 124 non-T/T carriers, respectively. The favorable association between T/T carriers' status and survival was significant in the multivariate analysis (P=0.018). Also, T/T carriers and non-T/T carriers were prevalent among patients with Karnofsky performance status 90-100 and 70-80, respectively (P=0.002). These findings encourage additional studies in this field and the evaluation of a recombinant-IL-1RA for anticancer activity.


Subject(s)
Colorectal Neoplasms/genetics , Interleukin 1 Receptor Antagonist Protein/genetics , Polymorphism, Single Nucleotide , Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antineoplastic Agents/therapeutic use , Cetuximab , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Disease-Free Survival , Female , Genotype , Humans , Interleukin 1 Receptor Antagonist Protein/blood , Karnofsky Performance Status , Male , Middle Aged , Multivariate Analysis , Neoplasm Invasiveness
6.
Br J Cancer ; 99(9): 1402-7, 2008 Nov 04.
Article in English | MEDLINE | ID: mdl-18971936

ABSTRACT

No established second-line chemotherapy is available for patients with advanced gastric cancer failing to respond or progressing to first-line chemotherapy. However, 20-40% of these patients commonly receive second-line chemotherapy. We evaluated the influence of clinico-pathologic factors on the survival of 175 advanced gastric cancer patients, who received second-line chemotherapy at three oncology departments. Univariate and multivariate analyses found five factors which were independently associated with poor overall survival: performance status 2 (hazard ratio (HR), 1.79; 95% CI, 1.16-2.77; P=0.008), haemoglobin 50 ng ml(-1) (HR, 1.86; 95% CI, 1.21-2.88; P=0.004), the presence of greater than or equal to three metastatic sites of disease (HR, 1.72; 95% CI, 1.16-2.53; P=0.006), and time-to-progression under first-line chemotherapy

Subject(s)
Stomach Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoembryonic Antigen/analysis , Disease Progression , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Stomach Neoplasms/mortality
7.
Br J Cancer ; 99(5): 716-21, 2008 Sep 02.
Article in English | MEDLINE | ID: mdl-18728661

ABSTRACT

We investigated the association between thymidylate synthase (TS) germline polymorphisms and response to 5-fluorouracil-based chemotherapy in 80 patients with liver-only metastatic colorectal cancer (MCRC). The tandem repeat polymorphism (VNTR) in TS 5'-untranslated region (5'-UTR), which consists of two (2R) or three (3R) 28-bp repeated sequences, with or without a G/C nucleotide change in 3R carriers (3G or 3C) and a 6-bp insertion/deletion (6+/6-) in the TS 3'-UTR, was studied. The distinction between high (2R/3G, 3C/3G and 3G/3G) and low (2R/2R, 2R/3C and 3C/3C) TS expression genotypes according to the 5'-UTR VNTR+G/C nucleotide change showed significant association with tumour response (P=0.01). In particular, high TS expression genotypes were found in 8 out of 34 patients (23.5%) with complete or partial response and in 24 out of 46 patients (52%) with stable disease and disease progression. Liver-only MCRC patients are a homogeneous and clinical relevant subgroup that may represent an ideal setting for studying the actual influence of TS polymorphisms.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Colorectal Neoplasms/drug therapy , Fluorouracil/therapeutic use , Liver Neoplasms/secondary , Polymorphism, Genetic , Thymidylate Synthase/genetics , Colorectal Neoplasms/enzymology , Colorectal Neoplasms/pathology , Female , Genotype , Haplotypes , Humans , Liver Neoplasms/drug therapy , Liver Neoplasms/enzymology , Male , Survival Analysis , Tandem Repeat Sequences , Treatment Outcome
8.
Pharmacogenomics J ; 8(4): 278-88, 2008 Aug.
Article in English | MEDLINE | ID: mdl-17549067

ABSTRACT

The primary end point of the study was the analysis of associations between polymorphisms with putative influence on 5-fluorouracil/irinotecan activity and progression-free survival (PFS) of patients with advanced colorectal cancer treated with first-line FOLFIRI chemotherapy. Peripheral blood samples from 146 prospectively enrolled patients were used for genotyping polymorphisms in thymidylate synthase (TS), methylenetetrahydrofolate reductase (MTHFR), excision repair cross-complementation group-1 (ERCC 1) xeroderma pigmentosum group-D (XPD), X-ray cross-complementing-1 (XRCC 1), X-ray cross-complementing-3 (XRCC 3) and uridine diphosphate-glucuronosyltransferases-A1 (UGT1 A1). TS 3'-UTR 6+/6+ and XRCC3-241 C/C genotypes were associated with adverse PFS. Hazard ratio for PFS achieved 2.89 (95% confidence interval=1.56-5.80; P=0.002) in 30 patients (20%) with both risk genotypes. Risk for Grade III-IV neutropenia was significantly associated with UGT1A1*28 7/7 genotype. These promising findings deserve further investigations and their validation in independent prospective studies.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Gene Expression Profiling/methods , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Camptothecin/analogs & derivatives , Camptothecin/pharmacology , Camptothecin/therapeutic use , Disease-Free Survival , Female , Fluorouracil/pharmacology , Fluorouracil/therapeutic use , Genotype , Humans , Irinotecan , Leucovorin/pharmacology , Leucovorin/therapeutic use , Male , Middle Aged , Pharmacogenetics/methods , Polymorphism, Genetic/drug effects , Polymorphism, Genetic/genetics , Prospective Studies
9.
Minerva Med ; 93(4): 303-7, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12207200

ABSTRACT

BACKGROUND: Anthracyclines combined with paclitaxel are one of the most active schedules in patients with advanced breast cancer: response rates range from 40 to 80%, considering all metastatic sites (visceral and soft tissues). We performed a non-randomized phase II trial with anthracyclines/paclitaxel combination to evaluate response and toxicity only in patients with visceral metastases. METHODS: Twenty-seven patients (median age 50 years; range 30-72) with visceral metastases of breast cancer were enrolled in this study. Overall, 11 patients had lung metastases (41%), 10 liver (37%), 4 liver-lung metastases (15%) and 2 peritoneal carcinosis (7%). 7 patients had received adjuvant anthracycline-based chemotherapy (26%) and 10 patients adjuvant CMF combination chemotherapy (37%); 10 patients (37%) received hormonal therapy for advanced disease. Treatment schedules were: group A) 17 patients, Adriamicyn 50 mg/m2 on day 1 i.v. bolus and Paclitaxel 175 mg/m2 on day 2 i.v. 3 hours infusion, every 3 weeks; group B) 10 patients, epirubicin 90 mg/m2 on day 1 i.v. bolus and paclitaxel 200 mg/m2 on day 2 i.v., 3 hours infusion, every 3 weeks. The number of cycles administered was 141 with a median of 5 (range 3-9). RESULTS: All patients were evaluable for response and toxicity. The objective response rate was 59% - 16 patients - (15% complete and 44% partial remission), 95% C.I. 40.7-77%; 10/17 in group A and 7/10 in group B. Stable disease 30% (8 patients) and progressive disease 11% (3 patients). The median duration of response was 5 months (range 1-16); median time to progression 13 months (range 3-18) and median survival 17 months (range 4-24). The main toxicity was neutropenia, occurred in 16 patients (59%; grade IV in 7 patients, of whom 2 febrile neutropenia, and grade III in 9 patients); grade III gastrointestinal toxicity in 2 patients; grade III neurological toxicity in 1 patient; grade III stomatitis in 2 patients. No congestive hearth failure or treatment death related was observed. CONCLUSIONS: These schedules of anthracyclines and paclitaxel confirmed their efficacy in metastatic breast cancer even in patients with visceral disease. Neutropenia was the main toxicity; grade IV neutropenia was more frequently observed in epirubicin/paclitaxel arm.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Liver Neoplasms/drug therapy , Lung Neoplasms/drug therapy , Peritoneal Neoplasms/drug therapy , Adult , Aged , Antibiotics, Antineoplastic/administration & dosage , Doxorubicin/administration & dosage , Epirubicin/administration & dosage , Female , Humans , Liver Neoplasms/secondary , Lung Neoplasms/secondary , Middle Aged , Paclitaxel/administration & dosage , Peritoneal Neoplasms/secondary
10.
Anticancer Res ; 22(5): 3087-92, 2002.
Article in English | MEDLINE | ID: mdl-12530048

ABSTRACT

BACKGROUND: Cisplatin/gemcitabine are one of the "standard" chemotherapy schedules in locally advanced and metastatic NSCLC cancer. A number of trials documented that omission of gemcitabine on day 15 and reduction of cisplatin up to 70 mg/mq are equivalent in term of response rates to "classic" administrations on days 1, 8 and 15 with cisplatin 100 mg/mq. The aim of this study was to confirm this evidence and to demonstrate that a further reduction of gemcitabine dose-intensity may be performed with the same efficacy on response. PATIENTS AND METHODS: Fifty untreated patients with locally advanced and metastatic NSCLC entered the study: 24 stage IIIB and 26 stage IV. The median age was 65 years (range 32-76); 44 males and 6 females Genicitabine was administered 1000 mg/mq weekly on days 1 and 8 followed by a 2-week rest and cisplatin 80 mg/mq on day 2 of each 28-day-cycle. RESULTS: Forty-five patients were evaluable for response and all for toxicity. The overall response rates were 35.5% with 16 partial responses (95% Confidence Interval: 32%-61%). Most of the objective responses were seen in IIIB patients (56% of the stage IIIB and 44% of the stage IV patients responded). According to the intent-to-treat-principle, the response rates were 32% (16 out of 50 patients). The median dose-intensity of gemcitabine and cisplatin was respectively 477.6 mg/mq/week (481.4 for responders) and 19.5 mg/mq/week (19.9 mg/mq for responders). The median response duration was 5 months (range 1-18) and the median time to progression was 5 months (1-21); median survival was 9 months (range 2-31). The main toxicity was haematological: thrombocytopenia grade IV in 5 patients (10%) and grade III in 11 patients (22%); neutropenia grade III-IV in 4 patients (8%); grade III anemia in 3 (6%). Asthenia was the most significant non-haematological toxicity and was observed in 19 patients (38%). CONCLUSION: This trial confirmed the efficacy of a schedule with 2 administrations of gemcitabine (on days 1, 8) and a cisplatin dose on day 2 lower than 100 mg/mq. Moreover, the same efficacy was obtained with a median-dose intensity of cisplatin and gemcitabine lower than planned in a 21-day-schedule. For safety and low toxicity, we think that this schedule provides another chance to treat patients with non-small cell lung cancer, especially the elderly or patients with coexistent medical illnesses.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Deoxycytidine/analogs & derivatives , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Staging , Survival Rate , Gemcitabine
11.
Cancer Invest ; 18(5): 411-6, 2000.
Article in English | MEDLINE | ID: mdl-10834024

ABSTRACT

Calcium and antioxidant vitamins, such as A, C, and E, have been shown to reduce colorectal epithelial proliferation and thereby to act as possible chemoprotective agents in colorectal cancer. We investigated the effects of an intervention with calcium and vitamins on cell proliferation in the colonic mucosa of patients operated on for colorectal cancer. Patients with resected colorectal cancer Dukes' stage B-C were randomized to receive daily 30,000 IU of axerophthol palmitate (vitamin A) plus 1 g ascorbic acid (vitamin C) plus 70 mg of dl-alpha-tocopherol acetate (vitamin E) and 2 g natural calcium daily or indistinguishable placebo for 6 months. At the time of surgery and after 6 and 12 months of treatment, cell kinetics of normal colonic mucosa were assessed by using proliferating cell nuclear antigen (PCNA). Ninety patients were enrolled and 77 were assessable: 34 in the treatment group and 43 in the placebo group. A significant reduction of mean total PCNA labeling index (PCNALI) was evident in both groups after 6 months (vitamins/calcium, from 16.11 +/- 2.43 to 10.71 +/- 2.81; placebo, from 17.30 +/- 2.63 to 12.53 +/- 3.40). The difference in the percentage of reduction of mean PCNALI between baseline and after 6 months was not statistically significant in the treatment and placebo groups: 34% and 28%, respectively. A second control, 6 months after discontinuation of vitamin and calcium supplementation, showed a further decrease of mean total PCNALI in both groups, but this was not statistically significant. Our randomized trial showed that calcium and vitamin supplementation does not reduce cell kinetics of colon epithelium. Furthermore, this study suggests the need for extreme caution in the interpretation and publication of studies on chemoprotectants in colon cancer without a control group.


Subject(s)
Ascorbic Acid/pharmacology , Calcium/pharmacology , Colorectal Neoplasms/prevention & control , Vitamin A/pharmacology , Vitamin E/pharmacology , Adult , Aged , Aged, 80 and over , Ascorbic Acid/administration & dosage , Calcium/administration & dosage , Cell Division/drug effects , Chemoprevention , Colorectal Neoplasms/pathology , Colorectal Neoplasms/physiopathology , Double-Blind Method , Female , Humans , Intestinal Mucosa/cytology , Intestinal Mucosa/drug effects , Kinetics , Male , Middle Aged , Vitamin A/administration & dosage , Vitamin E/administration & dosage
12.
J Exp Clin Cancer Res ; 19(1): 13-6, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10840930

ABSTRACT

We report the long-term results of a series of patients affected by advanced epithelial ovarian cancer treated with the PEC combination (cisplatin 60 mg/m2, epirubicin 60 mg/m2 and cyclophosphamide 750 mg/m2, all at day 1, every 21 days). Response was evaluated after three cycles, and treatment continued in responsive patients. A total of 80 patients with a median follow-up of 55 months were studied. Fifty-eight patients with stage III ovarian cancer and 22 patients with stage IV received PEC as primary treatment (41 patients), or for residual disease after surgery (37 patients), or for relapsed disease after primary surgery (2 patients). The overall response rate was 67.5% (20.0% complete response, 47.5% partial response), with 22.5% stable disease and 3.7% progressive disease. Median progression free survival was 13.0 months, and median survival was 25 months. Grade III-IV toxicity was moderate: leukopenia 20.0% of patients, thrombocytopenia 5.0%, anemia 16.2%. No cardiac toxicity was observed. In conclusion, the PEC combination, an anthracycline-containing platinum-based regimen, proved to be effective in advanced ovarian cancer, in terms of response rate and overall survival. The regimen was devoid of significant toxicity and in particular of cardiac toxicity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cisplatin/administration & dosage , Cyclophosphamide/administration & dosage , Epirubicin/administration & dosage , Ovarian Neoplasms/drug therapy , Adult , Aged , Combined Modality Therapy , Female , Humans , Middle Aged , Neoplasm, Residual/drug therapy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Recurrence , Retrospective Studies , Survival Analysis
13.
Support Care Cancer ; 6(2): 139-43, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9540173

ABSTRACT

Cancer patients with painful osteolytic bone metastases who had failed initial treatment with hormones and/or chemotherapy were each randomized to receive one of three pamidronate doses as outpatients: 45, 60, 90 mg given every 3 weeks for 12 weeks. Seventy patients were enrolled in this study, for a total of 265 infusions. There were 64 patients who completed 12 weeks of therapy. Forty-eight patients took nonsteroidal antinflammatory drugs, while 22 patients received morphine before pamidronate treatment. A reduction in bone pain and mobility scores was observed in all three different dose groups: in 11 of 23 patients (47%) at 45 mg; in 12 of 24 patients (50%) at 60 mg; and in 16 of 23 patients (69%) at 90 mg. However, while for patients receiving pamidronate at 90 mg median changes in pain and mobility were statistically significant at the 6th week, for patients receiving 45 mg they were not significant until the 12th week and for patients receiving 60 mg, until the 9th week. In weeks 0-6, the daily consumption of analgesics was reduced in 3 patients in the 45-mg arm, in 4 patients in the 60-mg arm, and in 7 patients in the 90-mg arm. In weeks 7-12, the daily consumption of analgesics was reduced in 8 patients receiving 45 mg, in 8 patients receiving 60 mg, and in 7 patients receiving 90 mg. No significant toxicity was recorded. In 2 patients (45 and 90 mg) fever (> 38 degrees C) and myalgia were observed after the first administration. In conclusion, our results seem to confirm the utility of higher doses of pamidronate in patients with painful bone metastases, because of the faster symptom relief achieved.


Subject(s)
Antineoplastic Agents/administration & dosage , Bone Neoplasms/secondary , Carcinoma/secondary , Diphosphonates/administration & dosage , Pain, Intractable/etiology , Adult , Aged , Female , Humans , Male , Middle Aged , Pain, Intractable/therapy , Pamidronate , Treatment Outcome
14.
J Clin Oncol ; 15(11): 3313-9, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9363860

ABSTRACT

PURPOSE: A multiinstitutional trial was performed to confirm the clinical activity, in terms of response rate and toxicity (primary objectives) and duration of responses and survival (secondary objectives), of an intensive weekly regimen in advanced gastric cancer. PATIENTS AND METHODS: Patients with measurable unresectable and/or metastatic gastric carcinoma received 1-day per week administration of cisplatin (CDDP) 40 mg/m2, fluorouracil (5FU) 500 mg/m2, epi-doxorubicin (epi-ADR) 35 mg/m2, 6S-stereoisomer of leucovorin 250 mg/m2, and glutathione 1.5 g/m2. On the other days, filgrastim was administered by subcutaneous injection at a dose of 5 mg/kg. One cycle of therapy consisted of eight 1-week treatments. Patients who showed a response or stable disease received a further 6 weeks of therapy. RESULTS: Of 105 enrolled patients, 11 had locally advanced unresectable disease only; 33 had primary nonresected and metastatic disease; 48 had metastatic disease and primary tumor resected; 10 had locoregional recurrence and metastatic disease; and three had locoregional recurrence only. After one cycle, 18 complete responses (CRs) and 47 partial responses (PRs) were achieved, for an overall response rate of 62% (95% confidence interval [CI], 53% to 71%). Twenty patients had stable disease and 20 progressed on therapy. The median survival duration of all 105 patients was 11 months, with 1- and 2-year survival rates of 42% and 5%, respectively. World Health Organization (WHO) grade III to IV toxicity, in terms of anemia, neutropenia, thrombocytopenia, and mucositis, was experienced by 40 patients (38%). There were no treatment-related deaths. CONCLUSION: These data support the results of the pilot study and confirmed the high activity of the regimen, with acceptable toxicity. This schedule deserves evaluation in the adjuvant setting.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Stomach Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Neoplasm Metastasis , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Survival Analysis
15.
Cancer Chemother Pharmacol ; 38(4): 385-6, 1996.
Article in English | MEDLINE | ID: mdl-8674163

ABSTRACT

A total of 26 patients with advanced colorectal cancer received 60 mg/m2 methotrexate i.v. on days 1-4; 400 mg/m2 5-fluorouracil i.v. on days 2, 3, 5, and 6; and 100 mg/m2 6S-leucovorin i.v. on days 2, 3, 5, and 6. Interferon-alpha 2b at a dose of 3 million U was given i.m. daily for the 6 days of chemotherapy. Courses were repeated every 3 weeks. There were four partial responses for a response rate of 15% (95% confidence interval 2-28%): In all, 14 patients expressed grade 3 toxicity; 9 patients had diarrhea, 3 had stomatitis, and 2 developed leukopenia. In conclusion, multimodal biochemical modulation of 5-fluorouracil, at least on this schedule, does not seem to be effective, as it results in severe toxicity.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Drug Administration Schedule , Feasibility Studies , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Interferon alpha-2 , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Leucovorin/administration & dosage , Leucovorin/adverse effects , Male , Methotrexate/administration & dosage , Methotrexate/adverse effects , Middle Aged , Pilot Projects , Recombinant Proteins , Remission Induction
16.
Support Care Cancer ; 4(1): 31-3, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8771291

ABSTRACT

In an open prospective study. 40 patients with progressing painful bone metastases received 45 mg pamidronate by 1-h infusion every 3 weeks. A total of 27 patients (67%; 95% CI 53%-81%) experienced relief of pain as shown by the significant reduction of the bone pain score after three pamidronate administrations (from 2.25 +/- 0.64 to 1.15 +/- 0.36). Furthermore, 20 patients (60%) reduced their consumption of analgesics. We did not observe any objective response by skeletal radiological examination. In 11 patients presenting a skeletal progressive disease, bone pain improved, as well as their mobility score, but not their fatigue score. Treatment was well tolerated. Only 1 patient discontinued the treatment because of fever and cutaneous rash after the first administration. In conclusion, our results seem to confirm that pamidronate exerts a benefical effect on bone pain and mobility impairment in patients with painful osteolytic bone metastases.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Agents/therapeutic use , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Diphosphonates/therapeutic use , Pain/drug therapy , Adult , Aged , Bone Neoplasms/physiopathology , Female , Humans , Male , Middle Aged , Pain/etiology , Palliative Care , Pamidronate , Prospective Studies
17.
Oncology ; 52(5): 422-6, 1995.
Article in English | MEDLINE | ID: mdl-7637961

ABSTRACT

The efficacy of recombinant human erythropoietin (rHuEPO) on the increase in hemoglobin levels was assessed in patients with cisplatin (CDDP)-induced anemia older than 70 years. Furthermore, we compared the results obtained in this group of patients with those observed in other patients receiving rHuEPO for a CDDP-associated anemia with similar clinical features (chemotherapeutic regimen, primary tumor; CDDP cumulative dose) but of an age less than 70 years. Twenty patients older than 70 years with a CDDP-associated anemia (hemoglobin levels < 90 milligrams) received rHuEPO at the dose of 100 U/kg subcutaneously, three times a week. The control group consisted of 20 younger patients, anemic after CDDP chemotherapy, treated with rHuEPO. All patients were evaluable for response and toxicity. Hemoglobin concentrations showed a statistically significant increase after the 3rd, 6th and 9th week of therapy in both older (93.1 +/- 10.7, 103.5 +/- 8.2 and 102.7 +/- 8.2, respectively, vs. baseline, 84.6 +/- 4.9) and younger patients (95.3 +/- 11.7, 101.5 +/- 13.4 and 101.9 +/- 8.7, respectively, vs. baseline, 86.6 +/- 4.0). Furthermore, 30% of older patients required blood transfusions versus 35% of younger patients, with the mean unit of blood transfused per patient being 0.7 U in elderly and 0.65 U in younger patients. Treatment was well tolerated with no significant side effects. The CDDP-induced anemia seems to be corrected by rHuEPO also in elderly patients, without differences with respect to younger patients.


Subject(s)
Anemia/drug therapy , Cisplatin/adverse effects , Erythropoietin/therapeutic use , Neoplasms/drug therapy , Adult , Age Factors , Aged , Anemia/chemically induced , Cisplatin/therapeutic use , Female , Humans , Male , Middle Aged , Recombinant Proteins/therapeutic use , Treatment Outcome
18.
Environ Health Perspect ; 102 Suppl 5: 251-2, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7882944

ABSTRACT

We report a prevalence study of environmental pleural plaques in subjects over 50 years old from the northeastern Corsican village of Murato, built on asbestos surface deposits. The percentage of plaques was 41%, versus 7.5% in the control village of Vezzani. Although surface deposits contain both chrysotile and tremolite, airborne pollution and asbestos lung burden of exposed inhabitants consist essentially of tremolite as assessed by transmission electron microscopy (TEM). However, TEM analysis of the parietal pleura of three animals bred in exposed areas showed a predominance of short fibers of chrysotile. The respective roles of tremolite and chrysotile in inducing pleural plaques in Corsica should thus be considered.


Subject(s)
Air Pollutants/adverse effects , Asbestosis/etiology , Minerals/analysis , Pleura/pathology , Aged , Animals , Asbestosis/epidemiology , Asbestosis/pathology , Dogs , Female , France/epidemiology , Goats , Humans , Male , Middle Aged , Pleura/metabolism , Prevalence
19.
Eur Respir J ; 6(7): 978-82, 1993 Jul.
Article in English | MEDLINE | ID: mdl-8396536

ABSTRACT

The purpose of this study was to determine whether the inhabitants of villages environmentally exposed to asbestos, in northeast Corsica, had a higher incidence of pleural plaques. X-rays were obtained from subjects aged over 50 yrs, with no occupational exposure to asbestos or history of pleural disease, in one village exposed to asbestos, Murato, and a nonexposed, control village, Vezzani. In addition, the mineral content of the air and parietal pleura of animals in the exposed zone was studied, using transmission electron microscopy. The incidence of bilateral pleural plaques in the exposed population was 41%, as compared to 7.5% in the nonexposed population (p < 0.00001). The levels of airborne tremolite were higher in Murato (6-72 ng.m-3) than in Vezzani (< 1 ng.m-3), but chrysotile levels were similar. Significant numbers of chrysotile and tremolite fibres were identified in the parietal pleura of animals from the exposed village. This study confirms the well-known correlation between bilateral pleural plaques and environmental exposure to low levels of asbestos.


Subject(s)
Asbestos, Amphibole , Asbestos , Asbestosis/epidemiology , Environmental Exposure , Pleural Diseases/epidemiology , Silicic Acid , Aged , Air Pollutants/analysis , Animals , Asbestos, Serpentine , Dogs , Female , France/epidemiology , Goats , Humans , Incidence , Male , Middle Aged , Pleura/chemistry , Prevalence
20.
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