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1.
Radiother Oncol ; 194: 110160, 2024 May.
Article in English | MEDLINE | ID: mdl-38369025

ABSTRACT

PURPOSE: The early regression index (ERI) predicts treatment response in rectal cancer patients. Aim of current study was to prospectively assess tumor response to neoadjuvant chemo-radiotherapy (nCRT) of locally advanced esophageal cancer using ERI, based on MRI. MATERIAL AND METHODS: From January 2020 to May 2023, 30 patients with esophageal cancer were enrolled in a prospective study (ESCAPE). PET-MRI was performed: i) before nCRT (tpre); ii) at mid-radiotherapy, tmid; iii) after nCRT, 2-6 weeks before surgery (tpost); nCRT delivered 41.4 Gy/23fr with concurrent carboplatin and paclitaxel. For patients that skipped surgery, complete clinical response (cCR) was assessed if patients showed no local relapse after 18 months; patients with pathological complete response (pCR) or with cCR were considered as complete responders (pCR + cCR). GTV volumes were delineated by two observers (Vpre, Vmid, Vpost) on T2w MRI: ERI and other volume regression parameters at tmid and tpost were tested as predictors of pCR + cCR. RESULTS: Complete data of 25 patients were available at the time of the analysis: 3/25 with complete response at imaging refused surgery and 2/3 were cCR; in total, 10/25 patients showed pCR + cCR (pCR = 8/22). Both ERImid and ERIpost classified pCR + cCR patients, with ERImid showing better performance (AUC:0.78, p = 0.014): A two-variable logistic model combining ERImid and Vpre improved performances (AUC:0.93, p < 0.0001). Inter-observer variability in contouring GTV did not affect the results. CONCLUSIONS: Despite the limited numbers, interim analysis of ESCAPE study suggests ERI as a potential predictor of complete response after nCRT for esophageal cancer. Further validation on larger populations is warranted.


Subject(s)
Esophageal Neoplasms , Magnetic Resonance Imaging , Neoadjuvant Therapy , Humans , Esophageal Neoplasms/therapy , Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/pathology , Male , Female , Prospective Studies , Middle Aged , Magnetic Resonance Imaging/methods , Aged , Chemoradiotherapy , Paclitaxel/administration & dosage , Carboplatin/administration & dosage , Treatment Outcome , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adult
2.
Blood Rev ; 45: 100730, 2021 01.
Article in English | MEDLINE | ID: mdl-32654893

ABSTRACT

In women with premature ovarian insufficiency (POI), hormonal therapy (HT) is indicated to decrease the risk of morbidity and to treat symptoms related to prolonged hypoestrogenism. While general recommendations for the management of HT in adults with POI have been published, no systematic suggestions focused on girls, adolescents and young women with POI following gonadotoxic treatments (chemotherapy, radiotherapy, stem cell transplantation) administered for pediatric cancer are available. In order to highlight the challenging issues specifically involving this cohort of patients and to provide clinicians with the proposal of practical therapeutic protocol, we revised the available literature in the light of the shared experience of a multidisciplinary team of pediatric oncologists, gynecologists and endocrinologists. We hereby present the proposals of a practical scheme to induce puberty in prepubertal girls and a decisional algorithm that should guide the clinician in approaching HT in post-pubertal adolescents and young women with iatrogenic POI.


Subject(s)
Hormone Replacement Therapy , Primary Ovarian Insufficiency/etiology , Primary Ovarian Insufficiency/therapy , Radiation Injuries/etiology , Radiation Injuries/therapy , Adolescent , Child , Clinical Decision-Making , Disease Management , Disease Susceptibility , Female , Hormone Replacement Therapy/methods , Humans , Puberty
3.
Clin Radiol ; 75(10): 798.e1-798.e11, 2020 10.
Article in English | MEDLINE | ID: mdl-32712007

ABSTRACT

AIM: To investigate the role of diffusion-weighted imaging (DWI), T2-weighted (W) imaging, and apparent diffusion coefficient (ADC) histogram analysis before, during, and after neoadjuvant chemoradiotherapy (CRT) in the prediction of pathological response in patients with locally advanced rectal cancer (LARC). MATERIALS AND METHODS: Magnetic resonance imaging (MRI) at 1.5 T was performed in 43 patients with LARC before, during, and after CRT. Tumour volume was measured on both T2-weighted (VT2W) and on DWI at b=1,000 images (Vb,1,000) at each time point, hence the tumour volume reduction rate (ΔVT2W and ΔVb,1,000) was calculated. Whole-lesion (three-dimensional [3D]) first-order texture analysis of the ADC map was performed. Imaging parameters were compared to the pathological tumour regression grade (TRG). The diagnostic performance of each parameter in the identification of complete responders (CR; TRG4), partial responders (PR; TRG3) and non-responders (NR; TRG0-2) was evaluated by multinomial regression analysis and receiver operating characteristics curves. RESULTS: After surgery, 11 patients were CR, 22 PR, and 10 NR. Before CRT, predictions of CR resulted in an ADC value of the 75th percentile and median, with good accuracy (74% and 86%, respectively) and sensitivity (73% and 82%, respectively). During CRT, the best predictor of CR was ΔVT2W (-58.3%) with good accuracy (81%) and excellent sensitivity (91%). After CRT, the best predictors of CR were ΔVT2W (-82.8%) and ΔVb, 1,000 (-86.8%), with 84% accuracy in both cases and 82% and 91% sensitivity, respectively. CONCLUSIONS: The median ADC value at pre-treatment MRI and ΔVT2W (from pre-to-during CRT MRI) may have a role in early and accurate prediction of response to treatment. Both ΔVT2W and ΔVb,1,000 (from pre-to-post CRT) can help in the identification of CR after CRT.


Subject(s)
Magnetic Resonance Imaging/methods , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Contrast Media , Diffusion Magnetic Resonance Imaging , Female , Humans , Male , Middle Aged , Neoadjuvant Therapy , Neoplasm Grading , Neoplasm Staging , Neoplasm, Residual/diagnostic imaging , Neoplasm, Residual/pathology , Organometallic Compounds , Rectal Neoplasms/therapy , Sensitivity and Specificity , Tumor Burden
4.
Colorectal Dis ; 21(9): 1017-1024, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31077550

ABSTRACT

AIM: The aim of this study was to assess the value of positron emission tomography (PET)/CT and sentinel lymph node (SLN) biopsy in staging inguinal lymph nodes in anal cancer patients and to determine if the results of the two methods could be of prognostic value. METHOD: Sixty-three patients with anal cancer and clinically negative inguinal lymph nodes underwent lymphoscintigraphy and inguinal SLN biopsy and/or fluorodeoxyglucose (FDG) PET/CT scan. All patients were treated with radiotherapy combined with 5-fluorouracil and mitomycin-C. RESULTS: Overall (OS) and disease-free survival (DFS) were 43 months (range 5-211) and 43 months (range 4-142) respectively. PET/CT examination showed high FDG uptake in the inguinal lymph nodes in 25% of patients. Thirty-five patients with inguinal uptake at lymphoscintigraphy underwent inguinal SLN biopsy and metastatic nodes were found in 31.4%. There was no statistical difference in OS (55 vs 41 months; P = 0.652) and DFS (48 vs 38 months; P = 0.992) between the group which showed inguinal uptake on PET/CT and the group which did not, while a positive inguinal SLN was associated with a worse OS (28 vs 59 months; P = 0.028) and DFS (56 vs 21 months; P = 0.046). When the two examinations were compared PET/CT showed a sensitivity, specificity, positive predictive value and negative predictive value of 22%, 82%, 33% and 73% respectively. CONCLUSION: The technique of SLN biopsy had a better diagnostic accuracy than total body FDG-PET/CT for the staging of inguinal lymph nodes in anal cancer patients; moreover it was a stronger predictor of OS and DFS than PET/CT.


Subject(s)
Anus Neoplasms/diagnostic imaging , Anus Neoplasms/pathology , Lymphatic Metastasis/pathology , Positron Emission Tomography Computed Tomography , Sentinel Lymph Node Biopsy , Aged , Anus Neoplasms/therapy , Combined Modality Therapy , Female , Fluorodeoxyglucose F18 , Humans , Inguinal Canal , Lymph Node Excision , Lymphoscintigraphy , Male , Middle Aged , Prognosis , Radiopharmaceuticals , Sensitivity and Specificity
5.
Clin Radiol ; 73(10): 911.e1-911.e7, 2018 10.
Article in English | MEDLINE | ID: mdl-30029837

ABSTRACT

AIM: To evaluate whether perfusion heterogeneity of rectal cancer prior to chemoradiotherapy (CRT) using histogram analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) quantitative parameters can predict response to treatment. MATERIALS AND METHODS: Twenty-one patients with histologically proven rectal adenocarcinoma were enrolled prospectively. All patients underwent 1.5 T DCE-MRI before CRT. Tumour volumes were drawn on Ktrans and Ve maps, using T2-weighted (W) images as reference, and the following first-order texture parameters of Ve and Ktrans values were extracted: 25th, 50th, 75th percentile, mean, standard deviation, skewness, and kurtosis. After CRT, patients underwent surgery and according with Rödel's tumour regression grade (TRG), they were classified as poor responders "non-GR" (TRG 0-2) and good responders "GR" (TRG 3-4). Differences between GR and non-GR in DCE-MRI first-order texture parameters were evaluated using the Mann-Whitney test, and their role in the prediction of response was investigated using receiver operating characteristic (ROC) curve analysis. RESULTS: Sixteen (76%) patients were classified as GR and five (24%) were non-GR. Skewness and kurtosis of Ve was significantly higher in non-GR (4.886±1.320 and 36.402±24.486, respectively) than in GR patients (1.809±1.280, p=0.003 and 6.268±8.130, p= 0.011). Ve skewness <3.635 was able to predict GR with an area under the ROC curve (AUC) of 0.988, sensitivity 93.8%, specificity 80%, and accuracy 90.5%. Ve kurtosis <21.095 was able to predict response with an AUC of 0.963, sensitivity 93.8%, specificity 80%, and accuracy 90.5%. Other parameters were not different between groups or predictors of response. CONCLUSION: Ve skewness and kurtosis seem to be promising in the prediction of response to CRT in rectal cancer patients.


Subject(s)
Rectal Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Chemoradiotherapy , Contrast Media , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Neoadjuvant Therapy , Prospective Studies , ROC Curve , Rectal Neoplasms/pathology , Retrospective Studies , Treatment Outcome
6.
Clin Radiol ; 73(6): 555-563, 2018 06.
Article in English | MEDLINE | ID: mdl-29459138

ABSTRACT

AIM: To investigate the potential role of an additional magnetic resonance imaging (MRI) examination performed during neoadjuvant chemoradiation therapy (CRT) in the prediction of pathological response in locally advanced rectal cancer (LARC). MATERIAL AND METHODS: Forty-eight consecutive patients with LARC underwent neoadjuvant CRT. MRI studies at 1.5 T, including high-resolution T2-weighted sequences that were acquired parallel and perpendicular to the main axis of the tumour were performed before (preMRI), during (midMRI), and 6-8 weeks after the end of CRT (postMRI). Cancer volumes (Vpre, Vmid, Vpost) were drawn manually and the reduction rate calculated (ΔVmid, ΔVpost). According to Rödel's pathological tumour regression grade (TRG), patients were considered non-responders (NR; TRG0-2), partial responders (PR; TRG3), and complete responders (CR; TRG4). Multivariate regression analysis was performed to identify the best MRI predictors of NR, PR, and CR. RESULTS: Twenty-five patients were considered PR (52%), 13 CR (27%), and 10 NR (22%). Tumour shrinkage mainly occurred shortly after CRT (ΔVmid: CR: 80±10% versus PR: 56±19% versus NR: 28±22%, p=2.2×10-16). Vmid, Vpost, ΔVmid, and ΔVpost correlated with TRG (p<0.001). At multivariate analysis, the combined assessment of Vmid and ΔVmid was selected as the best predictor of response to CRT, in that it distinguishes CR, PR, and NR early and accurately (81.5%). CONCLUSION: MidMRI allows final response assessment to neoadjuvant CRT earlier and better than the MRI performed after the end of CRT. MRI findings at midMRI may be useful to tailor patient treatment.


Subject(s)
Adenocarcinoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Rectal Neoplasms/therapy , Adenocarcinoma/pathology , Adult , Aged , Chemoradiotherapy, Adjuvant/methods , Drug Administration Schedule , Female , Fluorouracil/administration & dosage , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Oxaliplatin/administration & dosage , Prospective Studies , Rectal Neoplasms/pathology , Treatment Outcome , Tumor Burden
7.
Ann Oncol ; 28(11): 2786-2792, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-28945895

ABSTRACT

BACKGROUND: Patients with borderline (BL) or locally advanced (LA) pancreatic adenocarcinoma are usually treated with primary chemotherapy (CT), followed by resection when feasible. Scanty data are available about the criteria to candidate patients to resection after CT. PATIENTS AND METHODS: Between 2002 and 2016 overall 223 patients diagnosed with BL or LA pancreatic adenocarcinoma were primarily treated with Gemcitabine combination (4-drugs or nab-paclitaxel-gemcitabine) for 3-6 months followed by surgery and/or chemoradiation. Resection was carried out when radical resection could be predicted by imaging studies and intraoperative findings. The prognostic value of both pre-treatment factors and treatment response was retrospectively evaluated, searching for criteria that could improve the selection of patients for surgery. RESULTS: Median survival (MS) for the whole population was 18.3 months. Surgical resection was carried out in 61 patients; MS in resected patients was significantly longer (30.0 months) as compared with 162 non-resected patients (16.5 months) (P < 0.00001). According to response criteria, 48% had a radiological partial response, 47% a stable disease and 5% a disease progression); CA19.9 response (reduction >50%) was obtained in 77.8% of patients. Among resected patients, neither pre-treatment factors, including BL/LA distinction, nor radiological response, were able to prognosticate survival differences. Survival of resected patients having no CA19.9 response was significantly lower as compared with responders (MS 15.0 versus 31.5 months, P = 0.04), and was similar to non-responders patients that did not undergo resection (MS 10.9 months, P= 0.25). Multivariate analysis carried out on the overall population, showed that Karnofsky performance status, T3-T4 status, resection and CA19.9 response were independent prognostic factors, while radiological response, BL/LA distinction and baseline CA19.9 had not significant influence on survival. CONCLUSIONS: CA19.9 response may allow a better selection of patients who will benefit from resection after primary CT for BL or LA pancreatic adenocarcinoma.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatectomy , Pancreatic Neoplasms/drug therapy , Patient Selection , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoadjuvant Therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Prognosis , Retrospective Studies , Survival Rate , Pancreatic Neoplasms
8.
Cancer Chemother Pharmacol ; 64(6): 1253-9, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19381632

ABSTRACT

PURPOSE: The role and timing of chemotherapy and radiation for treating stage III pancreatic adenocarcinoma remains controversial. METHODS: Treatment-naive patients with stage III non-resectable pancreatic adenocarcinoma were treated with PEFG/PEXG (cisplatin, epirubicin, 5-fluorouracil (F)/capecitabine (X), gemcitabine) or PDXG (docetaxel substituting epirubicin) regimen for 6 months followed by radiotherapy (50-60 Gy) with concurrent F or X or G. RESULTS: Ninety-one patients were registered between April 1997 and December 2007. Forty-three patients (47%) had a partial remission and 38 (42%) had a stable disease. Thirteen patients (14%) were radically resected yielding one pathologic complete remission. Median survival (OS) was 16.2 months. Median progression-free survival was 9.9 months. Pattern of failure consisted of isolated local failure (N = 26, 35%); both local and systemic failure (N = 14, 19%); isolated systemic failure (N = 35, 47%). CONCLUSION: Combination chemotherapy with four-drug regimens followed by chemoradiation was a feasible strategy showing relevant results in stage III pancreatic adenocarcinoma.


Subject(s)
Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/radiotherapy , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Capecitabine , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cisplatin/therapeutic use , Combined Modality Therapy , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Disease Progression , Disease-Free Survival , Drug Therapy, Combination , Epirubicin/administration & dosage , Epirubicin/adverse effects , Epirubicin/therapeutic use , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Fluorouracil/therapeutic use , Humans , Male , Middle Aged , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Survival Analysis , Treatment Failure , Treatment Outcome , Gemcitabine
9.
Am J Clin Oncol ; 31(2): 145-50, 2008 Apr.
Article in English | MEDLINE | ID: mdl-18391598

ABSTRACT

OBJECTIVE: The therapeutic arsenal for salvage therapy in pancreatic cancer is limited. PEFG (cisplatin, epirubicin, 5-fluorouracil [FU], gemcitabine) regimen is an effective upfront treatment in advanced pancreatic cancer. The activity and safety of this combination regimen were assessed by means of an observational study in a population of patients with progressive or recurrent pancreatic adenocarcinoma after gemcitabine-containing chemotherapy. METHODS: Patients with age <76 years, Karnofsky performance status >50 were treated with either classic PEFG (until April 2004: cisplatin and epirubicin 40 mg/m day 1, gemcitabine 600 mg/m day 1 and 8, FU 200 mg/m/d continuous infusion day 1-28) or dose-intense PEFG (since May 2004: cisplatin and epirubicin 30 mg/m, gemcitabine 800 mg/m every 14 days; FU 200 mg/m/d continuous infusion day 1-28) until progressive disease or a maximum of 6 cycles of 28 days. RESULTS: Forty-six patients (37 metastatic) received 69 cycles of classic PEFG (18 patients) or 104 cycles of dose-intense PEFG (28 patients) as second-line therapy. Prior treatment consisted of single agent gemcitabine (N = 17), gemcitabine-based chemotherapy (N = 4), or PEFG regimen (N = 25). Median previous progression-free survival was 7.6 months. Dose intensity (mg/m/wk) with classic PEFG was cisplatin and epirubicin 8.5; gemcitabine 230; FU 1035 and with dose-intense PEFG was cisplatin and epirubicin 11.5 (+36%); gemcitabine 259 (+13%); FU 1046 (+1%). Main grade >2 toxicity consisted of neutropenia in 26 patients (56%), thrombocytopenia in 10 (22%), anemia in 11 (24%), fatigue and stomatitis in 4 (9%), vomiting, diarrhea and hand-foot syndrome in 2 (4%). Partial response was observed in 11 patients (24%) (5 classic PEFG 28% + 6 dose-intense PEFG 21%). Median and 1-year survival was 8.3 months (8.0 vs. 9.0 months) and 26% (17% vs. 32%). Median and 6-months progression-free survival was 5.0 months (4.5 vs. 5.0 months) and 34% (33% vs. 38%). CONCLUSIONS: PEFG regimen in gemcitabine refractory pancreatic cancer had an acceptable toxicity profile and interesting activity, and may constitute a treatment option in this setting.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Salvage Therapy , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Drug-Related Side Effects and Adverse Reactions , Epirubicin/administration & dosage , Epirubicin/adverse effects , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Humans , Male , Middle Aged , Pancreatic Neoplasms/pathology , Survival Analysis , Gemcitabine
10.
Cancer Invest ; 25(7): 594-8, 2007.
Article in English | MEDLINE | ID: mdl-17852117

ABSTRACT

The aim of this study was to assess the maximum tolerated dose (MTD) of an intensified PEFG regimen administered every 14 days to patients with Stage III or metastatic pancreatic adenocarcinoma. Twenty-nine patients received fixed doses of both epirubicin (30 mg/m2) and 5-fluorouracil (200 mg/m2/day on Days 1-14) and of escalating doses of cisplatin and gemcitabine. The MTD was cisplatin 30 mg/m2 and gemcitabine 800 mg/m2. With respect to classical PEFG, intensified regimen potentially improved the dose-intensity of both cisplatin and epirubicin by 50 percent and of gemcitabine by 33 percent, reduced Grade 3-4 haematological toxicity and the number of outpatient accesses.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Administration Schedule , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Male , Maximum Tolerated Dose , Middle Aged , Pancreatic Neoplasms/pathology , Gemcitabine
11.
Cancer Chemother Pharmacol ; 59(3): 361-7, 2007 Feb.
Article in English | MEDLINE | ID: mdl-16807732

ABSTRACT

BACKGROUND: PEFG regimen (cisplatin and epirubicin 40 mg/m2 day 1, gemcitabine 600 mg/m2 days 1 and 8, 5-fluorouracil (FU) 200 mg/m2/day continuous infusion) significantly improved the outcome of patients with advanced pancreatic adenocarcinoma (PA) with respect to standard gemcitabine in a previous phase III trial. This regimen was subsequently modified in a dose-finding study by increasing dose intensity of cisplatin and epirubicin (both at 30 mg/m2 every 14 days) and of gemcitabine (at 800 mg/m2 every 14 days). Results of a consecutive series treated by dose-intense PEFG regimen are herewith reported. MATERIAL AND METHODS: Dose-intense PEFG was administered to chemotherapy-naive patients with stages III-IV PA, < 75 years, performance status (PS) > 50, till progressive disease or for a maximum of 6 months. RESULTS: Between January 2004 and June 2005, 49 (31 or 63% metastatic) patients, median age 62 years, median PS 80, were treated with dose-intense PEFG. Partial response and stable disease was observed in 24 (49%) and 16 (33%) patients, respectively; 31 patients were progression-free at 6 months (PFS-6 = 63%). Median survival was 10.5 months and 1-year overall survival (OS) was 48% (95% confidence interval: 33-61%). Main grade 3-4 toxicity was: neutropenia in 26% of patients, stomatitis and fatigue in 8%, anaemia, diarrhoea, nausea/vomit in 6%, febrile neutropenia and thrombocytopaenia in 4%, hand-foot syndrome in 2%. CONCLUSION: When compared with 84 patients treated by classical PEFG at the same institution, dose-intense PEFG was not inferior in terms of PFS-6 (63 versus 57%), 1-year OS (48 versus 42%) and response rate (49 versus 49%); it allowed to increase dose intensity for gemcitabine by 32%, for cisplatin and epirubicin by 36% (FU reduced by 3%), to significantly reduce grade 3-4 hematological toxicity (neutropenia: 26 versus 86%; P < 0.00001; thrombocytopaenia: 4 versus 58%; P < 0.00001) and to reduce by one-third the number of outpatient accesses. The new PEFG schedule appears more suitable for clinical use and should be preferred as a basis for further development of therapeutic strategies against pancreatic cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Dose-Response Relationship, Drug , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Survival Rate , Gemcitabine
12.
Br J Cancer ; 94(6): 785-91, 2006 Mar 27.
Article in English | MEDLINE | ID: mdl-16508631

ABSTRACT

Limited information on salvage treatment in patients affected by pancreatic cancer is available. At failure, about half of the patients present good performance status (PS) and are candidate for further treatment. Patients >18 years, PS >or=50, with metastatic pancreatic adenocarcinoma previously treated with gemcitabine-containing chemotherapy, and progression-free survival (PFS) <12 months received a combination of raltitrexed (3 mg m(-2)) and oxaliplatin (130 mg m(-2)) every 3 weeks until progression, toxicity, or a maximum of six cycles. A total of 41 patients received 137 cycles of chemotherapy. Dose intensity for both drugs was 92% of the intended dose. Main grade >2 toxicity was: neutropenia in five patients (12%), thrombocytopenia, liver and vomiting in three (7%), fatigue in two (5%). In total, 10 patients (24%) yielded a partial response, 11 a stable disease. Progression-free survival at 6 months was 14.6%. Median survival was 5.2 months. Survival was significantly longer in patients with previous PFS >6 months and in patients without pancreatic localisation. A clinically relevant improvement of quality of life was observed in numerous domains. Raltitrexed-oxaliplatin regimen may constitute a treatment opportunity in gemcitabine-resistant metastatic pancreatic cancer. Previous PFS interval may allow the identification of patients who are more likely to benefit from salvage treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Disease Progression , Drug Resistance, Neoplasm , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Neoplasm Metastasis , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Pancreatic Neoplasms/pathology , Quality of Life , Quinazolines/administration & dosage , Salvage Therapy , Survival Analysis , Thiophenes/administration & dosage , Gemcitabine
13.
Cancer Invest ; 22(5): 688-96, 2004.
Article in English | MEDLINE | ID: mdl-15581049

ABSTRACT

BACKGROUND: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. PATIENTS AND METHODS: Patients with less than 76 years, Karnofsky performance status > or = 60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m2 day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30 and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia > 7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade > or = 3 nonhematological toxicity, or failure to recover to grade < or = 1 toxicity by day 43, occurring during the first cycle of chemotherapy. RESULTS: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median survival was 1.7 and 6.1 months, respectively. CONCLUSION: The MTD was mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Camptothecin/analogs & derivatives , Pancreatic Neoplasms/drug therapy , Salvage Therapy , Adenocarcinoma/mortality , Adolescent , Adult , Aged , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/adverse effects , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/adverse effects , Camptothecin/administration & dosage , Camptothecin/adverse effects , Disease-Free Survival , Docetaxel , Female , Humans , Irinotecan , Male , Maximum Tolerated Dose , Middle Aged , Mitomycin/administration & dosage , Mitomycin/adverse effects , Pancreatic Neoplasms/mortality , Taxoids/administration & dosage , Taxoids/adverse effects , Treatment Outcome
14.
Lung Cancer ; 34(2): 279-87, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11679187

ABSTRACT

One-hundred and twenty-one cases of malignant pleural mesothelioma (MPM) seen between 1986 and 1999 at the authors' Institution were reviewed. Histotype was epithelial in 88 patients (73%), sarcomatous in 21 (17%) and mixed in 12 (10%). Ninety-one patients received a treatment (38 palliative pleurectomy and no further therapy, 16 palliative pleurectomy followed by chemotherapy, 37 chemotherapy alone), while 30 were referred to supportive care only. Median survival of the whole population was 10.5 months. The 1-, 2- and 3-year survival were 40, 17 and 8%, respectively. Univariate analysis of subgroups showed that poor performance status (PS), non-epithelial histotype, Butchart stage>I and International Mesothelioma Interest Group (IMIG) stage>I were individually associated with lower survival. Patients receiving any therapy survived longer than patients treated with supportive care only (P=0.0004). Treatment modality had an independent prognostic value (P=0.00005), with a survival advantage for patients receiving surgery and adjuvant chemotherapy. Multivariate analysis confirmed the independent prognostic value of PS (P=0.001; HR=2.48) and treatment modality (P=0.003; HR=1.38). The prognostic role of PS (P=0.02) and treatment modality (P=0.01) was confirmed in the subset of patients with epithelial histology. On the contrary, therapy had no impact on survival in patients with sarcomatoid MPM (P=0.74). Despite the predicted bias of a retrospective non-randomized evaluation of treatment-related factors, patients with good PS and epithelial histology seemed to have a survival benefit from surgery or multimodality therapy, as opposite to patients with poor PS or non-epithelial histotype. However, these results must be confirmed in a larger prospective trial with uniform treatment.


Subject(s)
Mesothelioma/pathology , Pleural Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Male , Mesothelioma/drug therapy , Mesothelioma/surgery , Middle Aged , Palliative Care , Pleural Neoplasms/drug therapy , Pleural Neoplasms/surgery , Prognosis , Retrospective Studies , Survival Analysis , Treatment Outcome
15.
Int J Radiat Oncol Biol Phys ; 50(3): 651-8, 2001 Jul 01.
Article in English | MEDLINE | ID: mdl-11395232

ABSTRACT

PURPOSE: To assess the impact on local control and survival of intraoperative radiotherapy (IORT) in resectable pancreatic adenocarcinoma. METHODS AND MATERIALS: The outcome of 127 patients surgically treated with curative intent combined with IORT was compared with the therapeutic results of 76 patients treated with surgery as exclusive treatment. RESULTS: Operative mortality and morbidity were similar in IORT and no-IORT patients. In 49 patients with locally limited disease (Stage I-II; LLD), IORT (n = 30) reduced the local failure rate and significantly prolonged time to local failure (TTLF), time to failure (TTF), and overall survival (OS) with respect to surgery alone (n = 19). The multivariate analyses, stratifying patients by age, tumor grade, resection margins, chemotherapy, and external-beam radiotherapy use, confirmed the independent impact of IORT on outcome. In patients with locally advanced disease (Stage III-IVA; LAD), IORT had an impact on local failure rate and on TTLF when combined with beam energies of greater than 6 MeV, whereas no effect on TTF and OS was observed. CONCLUSION: IORT did not increase operative mortality and morbidity and achieved a significant improvement in local control and outcome in patients with LLD. In patients with LAD, beam energies greater than 6 MeV prolonged TTLF.


Subject(s)
Adenocarcinoma/radiotherapy , Adenocarcinoma/surgery , Pancreatic Neoplasms/radiotherapy , Pancreatic Neoplasms/surgery , Adenocarcinoma/pathology , Adult , Aged , Combined Modality Therapy , Electrons , Female , Humans , Intraoperative Care , Male , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/pathology , Survival Rate , Treatment Outcome
16.
J Clin Oncol ; 19(10): 2679-86, 2001 May 15.
Article in English | MEDLINE | ID: mdl-11352960

ABSTRACT

PURPOSE: To evaluate the efficacy and toxicity of a cisplatin, epirubicin, gemcitabine, and fluorouracil (PEF-G) schedule on stage IV pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients < or = 70 years, with no prior chemotherapy and with bidimensionally measurable stage IV pancreatic adenocarcinoma, Eastern Cooperative Oncology Group performance status < or = 2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or Karnofsky performance status between 50 and 70. Treatment consisted of 40 mg/m2 each of cisplatin and epirubicin day 1, gemcitabine 600 mg/m2 on days 1 and 8 every 4 weeks, and fluorouracil 200 mg/m2/d as a protracted venous infusion. RESULTS: Between April 1997 and April 1999, 49 patients from a single institution were eligible for the study. Altogether, 203 cycles (median, four cycles) of PEF-G were delivered. The objective response rate was 58% in 43 assessable patients and 51% in the intent-to-treat population. Fourteen patients had stable disease. Grade 3 or 4 World Health Organization neutropenia occurred in 51% of cycles, thrombocytopenia in 28%, anemia in 7%, stomatitis in 5%, and diarrhea, and nausea, and vomiting in 2%. The median duration of response was 8.5 months. The median time to tumor progression was 7.5 months. The median survival was 11 months in the assessable population and 10 months in the intent-to-treat population. Clinical benefit was achieved in 22 (78%) of 28 assessable patients. CONCLUSION: PEF-G is a well-tolerated and safe regimen; it obtained a very high rate of durable responses and deserves further evaluation in a phase III trial.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Antibiotics, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Administration Schedule , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Male , Middle Aged , Neoplasm Metastasis , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Treatment Outcome , Gemcitabine
17.
Cancer ; 89(1): 89-96, 2000 Jul 01.
Article in English | MEDLINE | ID: mdl-10897005

ABSTRACT

BACKGROUND: The combination of paclitaxel and epirubicin has shown a favorable interaction in patients with advanced breast carcinoma. Therefore the efficacy and toxicity of this regimen was evaluated in a Phase II study of patients with metastatic nonsmall cell lung carcinoma (NSCLC). METHODS: Thirty-two chemotherapy-naive patients with AJCC Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were entered into the study. Patients received epirubicin, 90 mg/m(2), followed by paclitaxel, 175 mg/m(2) by 3-hour infusion, on Day 1. The treatment was repeated every 3 weeks. Granulocyte-colony stimulating factor (G-CSF) was not used routinely. RESULTS: A total of 116 treatment cycles was delivered. All patients could be assessed for response, toxicity, and survival. There were 16 partial responses and no complete responses, giving rise to an overall response rate of 50% (95% confidence interval, 31. 9-68.1%). The median time to progression in responders was 7 months. The median survival was 8 months, and the 1-year survival rate was 37%. World Health Organization Grade 4 neutropenia occurred in 69% of patients, but could be managed easily with G-CSF, which was used in 35% of cycles. Cumulative peripheral neuropathy was the main nonhematologic toxicity and was observed in 7 of 8 patients who received 6 treatment courses (Grade 2-3 in 3 cases) and in 6 of 11 patients who received 4 cycles (Grade 2 in 2 patients). One patient died shortly after the first course of chemotherapy from a ventricular arrhythmia. CONCLUSIONS: The combination of paclitaxel and epirubicin was found to be effective and well tolerated in chemotherapy-naive patients with metastatic NSCLC and warrants further evaluation in a multicenter trial of a larger number of patients. Careful cardiac evaluation before treatment is indicated.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Disease Progression , Disease-Free Survival , Epirubicin/administration & dosage , Female , Humans , Infusions, Intravenous , Lung Neoplasms/pathology , Male , Middle Aged , Paclitaxel/administration & dosage , Treatment Outcome , Ventricular Fibrillation/chemically induced
18.
Am J Clin Oncol ; 22(5): 460-5, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10521059

ABSTRACT

Primary cardiac sarcoma (PCS) is a rare disease with a poor prognosis, because of diagnostic delay, therapeutic difficulties, and high metastatic potential. Surgery is the standard treatment. A case of PCS in pregnancy is reported, with a review of published surgical series of PCSs, focusing on the role of surgery and adjuvant therapy. Prompt surgery improved cardiac function and patients' outcome in comparison with untreated cases. The role of adjuvant treatment was analyzed only in a few series, mainly without distinction between postoperative chemotherapy and radiotherapy; adjuvant therapy improved survival in the larger series of resected PCSs. Only three other cases of PCS in pregnancy were reported. In the present case, resection was performed with no major complication for the mother and the infant. Even if the patient's survival was short, cardiac surgery allowed prolonging of pregnancy until an acceptable possibility of fetal survival was reached. Although resection is not curative in most cases, surgery remains the treatment of choice for PCS and has a definite palliative significance. The role of postoperative chemotherapy and radiotherapy is difficult to ascertain; however, adjuvant chemotherapy seems advisable in high-grade tumors.


Subject(s)
Heart Neoplasms/complications , Pregnancy Complications, Neoplastic , Sarcoma/complications , Adult , Chemotherapy, Adjuvant , Female , Heart Neoplasms/mortality , Heart Neoplasms/pathology , Heart Neoplasms/surgery , Humans , Pregnancy , Pregnancy Complications, Neoplastic/mortality , Pregnancy Complications, Neoplastic/pathology , Pregnancy Complications, Neoplastic/surgery , Pregnancy Outcome , Radiotherapy, Adjuvant , Sarcoma/mortality , Sarcoma/pathology , Sarcoma/surgery , Survival Rate
20.
Cancer Treat Rev ; 19 Suppl C: 3-9, 1993.
Article in English | MEDLINE | ID: mdl-8221714

ABSTRACT

Carboplatin, a platinum analog with single-agent activity in previously untreated breast cancer, is characterized by comparatively less renal toxicity and emesis than cisplatin. We combined carboplatin at different dose levels [from 200 to 350 mg/m2 by intravenous (IV) infusion on day 1] with 5-fluorouracil (500 mg/m2 IV on days 1 and 8) and cyclophosphamide (500 mg/m2 IV on day 1), with all three drugs recycled every 28 days, to evaluate anti-tumor activity and toxicity of this novel combination [5-fluorouracil/carboplatin/cyclophosphamide (FCC)] in untreated locally advanced (LABC) or metastatic breast cancer (M+). Of 37 patients treated between March 1990 and August 1991 [LABC 25, M+ 8; World Health Organization (WHO) performance status, 0-1; median number of treatment cycles, 5; median follow-up, 20 months], 33 are evaluable for response and toxicity. The overall complete plus partial remission rate was 57% (LABC 68%, M+ 25%). The median duration of response was 19+ months. The cumulative carboplatin dose ranged from 800 to 2350 mg/m2 (median, 1450 mg/m2). In this series, no correlation was observed between the carboplatin dose level and response rate or toxicity. Leukopenia and thrombocytopenia represented the most frequent toxicities. WHO grades 3 and 4 neutropenia were documented in 34% and 8% of patients, respectively. Thrombocytopenia below 50 x 10(9)/l was observed in 8%. No renal toxicity was observed, and moderate emesis occurred in 67% of patients. These results indicate that FCC is an active and relatively safe combination for the treatment of advanced breast cancer in patients not previously treated with chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Carboplatin/administration & dosage , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/adverse effects , Cyclophosphamide/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Methotrexate/administration & dosage , Middle Aged , Neutropenia/chemically induced , Thrombocytopenia/chemically induced
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