Prognostic factors in elderly patients with malignant pleural mesothelioma: results of a multicenter survey.

BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. There are no specific guidelines for their management. METHODS: The clinical records of elderly patients (⩾70 years old) with MPM referred from January 2005 to November 2011 to six Italian Centres were reviewed. Age, gender, histology, International Mesothelioma Interest Group (IMIG) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and treatment modalities were analysed and correlated to overall survival (OS). RESULTS: In total, 241 patients were identified. Charlson Comorbidity Index was ⩾1 in 92 patients (38%). Treatment was multimodality therapy including surgery in 18, chemotherapy alone in 180 (75%) and best supportive care in 43 cases (18%). Chemotherapy was mainly pemetrexed based. Median OS was 11.4 months. Non-epithelioid histology (HR 2.32; 95% CI 1.66-3.23, P<0.001), age ⩾75 years (HR 1.44; 95% CI 1.08-1.93, P=0.014), advanced (III-IV) stage (HR 1.47; 95% CI 1.09-1.98, P=0.011) and CCI⩾1 (HR 1.38; 95% CI 1.02-1.85, P=0.034) were associated to a shorter OS. Treatment with pemetrexed was associated with improved OS (HR 0.40; 95% CI 0.28-0.56, P<0.001). CONCLUSIONS: Non-epithelioid histology, age ⩾75 years, advanced IMIG stage and presence of comorbidities according to CCI were significant prognostic factors in elderly patients with MPM. Treatment with pemetrexed-based chemotherapy was feasible in this setting. Prospective dedicated trials in MPM elderly patients selected according to prognostic factors including comorbidity scales are warranted.

Phase II study of pemetrexed and carboplatin plus bevacizumab as first-line therapy in malignant pleural mesothelioma.

BACKGROUND: The aim of this open label phase II study (NCT00407459) was to assess the activity of the vascular endothelial growth factor (VEGF) inhibitor bevacizumab combined with pemetrexed and carboplatin in patients with previously untreated, unresectable malignant pleural mesothelioma (MPM). METHODS: Eligible patients received pemetrexed 500 mg m(-2), carboplatin area under the plasma concentration-time curve (AUC) 5 mg ml(-1) per minute and bevacizumab 15 mg kg(-1), administered intravenously every 21 days for six cycles, followed by maintenance bevacizumab. The primary end point of the study was progression-free survival (PFS). A 50% improvement in median PFS in comparison with standard pemetrexed/platinum combinations (from 6 to 9 months) was postulated. RESULTS: Seventy-six patients were evaluable for analysis. A partial response was achieved in 26 cases (34.2%, 95% CI 23.7-46.0%). Forty-four (57.9%, 95% CI 46.0-69.1%) had stable disease. Median PFS and overall survival were 6.9 and 15.3 months, respectively. Haematological and non-haematological toxicities were generally mild; however, some severe adverse events were reported, including grade 3-4 fatigue in 8% and bowel perforation in 4% of patients. Three toxic deaths occurred. CONCLUSION: The primary end point of the trial was not reached. However, due to the limitation of a non-randomised phase II design, further data are needed before drawing any definite conclusion on the role of bevacizumab in MPM.

Carboplatin and gemcitabine chemotherapy for malignant pleural mesothelioma: a phase II study of the GSTPV.

This study describes the therapeutic effect of carboplatin and gemcitabine in combination for malignant pleural mesothelioma (MPM). Twenty patients (14 males and 6 females) with a median age of 53 years entered the study. These patients had histologically proven MPM with no previous chemo- and/or radiotherapy and malignancies. A total of 91 cycles of treatment were administered to 20 patients with a median of 4 cycles per patient. A partial response was observed in 4 out of 20 patients (20%, 95% confidence interval: 6-43%). No complete responses were observed. Only 5 patients (25%) had progressive disease. The response duration ranged form 4+ and 21 months.

Phase II randomized study of dacarbazine, carmustine, cisplatin and tamoxifen versus dacarbazine alone in advanced melanoma patients.

This randomized phase II trial was performed to define the activity and toxicity of the combination of dacarbazine (DTIC), carmustine (BCNU), cisplatin (DDP) and tamoxifen (DBDT regimen) versus DTIC alone in patients with metastatic melanoma. Sixty patients with metastatic melanoma were randomly assigned to receive BCNU 150 mg/m2 intravenously (i.v.) on day 1, cisplatin 25 mg/m2 i.v. daily on days 1 to 3, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and tamoxifen 160 mg orally daily for 7 days prior to chemotherapy (DBDT arm; arm A). Treatment cycles were repeated every 28 days, while BCNU was given every two cycles. The DTIC arm (arm B) patients received DTIC alone 1200 mg/m2 i.v. on day 1, repeated every 21 days. Patients were evaluated every two cycles; responding patients continued the treatment for a maximum of 12 cycles. The overall response rate was 26% in the DBDT arm and 5% in the DTIC arm. Complete responses were 2.5% for DBDT and 0% for DTIC. The median progression-free survival and the median survival were 4 and 9 months, respectively for DBDT, and 2 and 7 months for DTIC. DBDT was associated with significant haematological toxicity: 33% of the patients experienced a grade III or IV neutropenia and 28% a grade III or IV thrombocytopenia. In conclusion, the overall response rate obtained with DBDT was greater than that obtained with DTIC alone; however, this combination increases toxicity with limited impact on overall survival.

Neoadjuvant moderately high-dose chemotherapy with rh-G-CSF in locally advanced breast carcinoma.

UNLABELLED: The poor results of local treatment for locally advanced breast carcinoma (LABC) justify the use of chemotherapy as primary treatment. Retrospective studies have shown a positive correlation between dose and response rate in advanced breast cancer. G-CSF has shown efficacy in achieving optimal dose intensity and ameliorating chemotherapy-induced myelosuppression. The aim of the present study was to assess the efficacy of a moderately high-dose chemotherapy regimen in terms of response rate, disease-free and overall survival and to assess the role of G-CSF in induced neutropenia. METHODS: Inclusion criteria were the following: age <65 years, WHO performance status <2, histologically proven breast carcinoma, adequate hematologic, renal and hepatic function, stage IIIA or IIIB disease, and no metastatic disease. No prior chemotherapy or radiotherapy was allowed. Three cycles of the following chemotherapy were used preoperatively: epirubicin (100 mg/m2 on day 1), cyclophosphamide (400 mg/m2 for 3 consecutive days) and rh-G-CSF (5 microg/kg/die from day 4 to day 12 every 14 days). After mastectomy or quadrantectomy plus radiotherapy, all patients were treated with 4 courses of adjuvant chemotherapy according to the CMF 1-8 schedule (methotrexate, 40 mg/m2 cyclophosphamide, 600 mg/m2; fluorouracil, 600 mg/m2; all on days 1 and 8, with recycle every 4 weeks). RESULTS: From May 1992 to June 1996, 57 patients with histologically proven LABC were preoperatively treated. Forty-four patients were premenopausal and 13 postmenopausal; the median age was 45 years (range, 29-64). Thirty-five patients had stage IIIA and 22 patients stage IIIB disease (7 with inflammatory disease). Forty-seven patients underwent radical mastectomy and 10 conservative surgery. A clinical response was noted in 93% (95% confidence interval, 83-98%) of patients (12% complete responses and 81% partial responses); 2 pathological complete remissions (3.5%) were obtained. No toxic deaths were observed. All patients had a follow-up of at least 42 months. The overall 5-year survival rate was 76% (standard error--SE), 6%) and the 5-year disease-free survival rate was 68% (SE, 6.3%). CONCLUSIONS: The 14-day regimen was well tolerated and effective in LABC patients, although not superior to standard-dose chemotherapy. To improve results the use of new drugs in controlled clinical trials seems warranted.