A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2-69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m(-2) i.v. day 1 and gemcitabine 1000 mg m(-2) i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20-46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life.     

Multicentre phase II study of gemcitabine and cisplatin in malignant pleural mesothelioma

Malignant pleural mesothelioma is a notoriously chemoresistant tumour. However, a recent single institution study showed an impressive activity of gemcitabine and cisplatin. Our aim is to investigate the efficacy and toxicity of a gemcitabine and cisplatin combination in selected and chemo-naive patients with histologically proven malignant pleural mesothelioma. METHOD: Gemcitabine 1250 mg m(-2) was administered on day 1 and day 8 and cisplatin 80 mg m(-2) was administered on day 1 in a 3-week cycle with a maximum of six cycles. Response and toxicity evaluations were performed according to WHO and NCIC-CTC criteria. Pathology and radiology were centrally reviewed. Results show that in 25 evaluable patients, four PR were observed (ORR 16%, 95% CI 1-31%). Responses of seven patients were unevaluable. No unexpected toxicity occurred. Time to progression was 6 months (5-7 months) with a median survival from registration of 9.6 months (95% CI 8-12 months). In conclusion this trial excludes with 90% power a response rate of greater than 30% in patients with malignant pleural mesothelioma using a combination of gemcitabine and cisplatin at the proposed dose and schedule.     

A phase 2 study of gemcitabine and epirubicin for the treatment of pleural mesothelioma: a North Central Cancer Treatment Study, N0021

BACKGROUND: The North Central Cancer Treatment Group (NCCTG) conducted a phase 2 study to evaluate the antitumor activity of the combination of gemcitabine and epirubicin in patients with pleural mesothelioma who received no more than 1 prior chemotherapy regimen. METHODS: A total of 23 patients were accrued between August 2001 and April 2002 and received gemcitabine at a dose of 1000 mg/m(2) intravenously over 30 minutes weekly every 2 weeks and epirubicin at a dose of 90 mg/m(2) intravenously on Day 1 on an every-21-days cycle (high-dose patient group). Between August 2002 and April 2004, an additional 45 patients were treated at a reduced dose of gemcitabine of 750 mg/m(2) and epirubicin at a dose of 70 mg/m(2) with the same schedule (low-dose patient group). RESULTS: In the high-dose patient group, the confirmed response rate was 13% (95% confidence interval [95% CI], 3-34%). The median survival was 9.3 months (95% CI, 7.4-10.7 months) and the median time to disease progression was 6.3 months (95% CI, 3.0-7.6 months). In the low-dose patient group, the confirmed response rate was 7% (95% CI, 0-28%). The median survival was 5.7 months (95% CI, 4.7-8.7 months) and the median time to disease progression was 4.2 months (95% CI, 2.7-5.6 months). Toxicity was moderate to severe. In the high-dose and low-dose groups, 87% and 60% of patients, respectively, experienced at least 1 adverse event of grade 4 or higher (according to National Cancer Institute Common Toxicity Criteria [version 2.0]). The quality of life remained similar from baseline to the end of the 2 cycles of treatment in the high-dose group but worsened in the low-dose group. CONCLUSIONS: In the current study, the combination regimen of gemcitabine and epirubicin was found to demonstrate minimal antitumor activity against pleural mesothelioma.     

Combination of raltitrexed and oxaliplatin is an active regimen in malignant mesothelioma: results of a phase II study.

PURPOSE: The aim of this open-label phase II study was to evaluate the activity of raltitrexed (Tomudex; AstraZeneca, Cergy, France) and oxaliplatin combination therapy in patients with diffuse malignant pleural mesothelioma. PATIENT AND METHODSs: Fifteen pretreated and 55 chemotherapy-naive patients (median age, 60 years; World Health Organization performance status of < or = 2) were enrolled. Most patients (66%) had advanced disease. Patients received raltitrexed 3 mg/m2 followed by oxaliplatin 130 mg/m2 every 3 weeks. RESULTS: Twenty-four patients (34%) were classified as having a poor prognosis. In the overall study population, 14 patients (20%) had a partial response, and 32 patients (46%) had stable disease. The symptomatic response rates were as follows: shortness of breath, 36%; pain, 30%; activity, 23%; appetite, 21%; and asthenia, 20%. Median time to disease progression was 18 weeks (95% confidence interval [CI], 13 to 22 weeks). In chemotherapy-naive patients, median survival was 31 weeks (95% CI, 23 to 40 weeks) from the start of treatment and 49 weeks (95% CI, 40 to 52 weeks) from diagnosis of mesothelioma. In pretreated patients, median survival was 44 weeks (95% CI, 24 to 40 weeks) from the start of treatment and 226 weeks (95% CI, 63 to 292 weeks) from the diagnosis of mesothelioma. Overall 1-year survival was 26% (95% CI, 15.5% to 36.4%), survival was 22% (95% CI, 10.9% to 33.2%) in chemotherapy-naive patients and 40% (95% CI, 15.2% to 64.8%) in pretreated patients. Hematologic toxicity was mild, and there was no alopecia. The most common adverse events were asthenia, nausea/vomiting, and paraesthesia, and no treatment-related deaths were reported. CONCLUSION: The raltitrexed and oxaliplatin combination is an active outpatient regimen in malignant mesothelioma and has an acceptable tolerability profile.     

Cisplatin and gemcitabine treatment for malignant mesothelioma: a phase II study.

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m2, given intravenously on day 1, and gemcitabine 1,000 mg/m2, given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.     

A Phase II study of gemcitabine in patients with malignant pleural mesothelioma. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.

BACKGROUND: Gemcitabine has shown activity in patients with less chemosensitive solid tumors. Phase II screening of novel drugs is an accepted method with which to investigate new therapies in malignant mesothelioma. The European Organization for Research and Treatment of Cancer-Lung Cancer Cooperative Group has performed several sequential Phase II trials of new agents for the treatment of mesothelioma over the last 10 years. METHODS: Twenty-seven chemotherapy-naive patients with histologically proven malignant mesothelioma were treated with gemcitabine as a 30-minute intravenous administration of 1250 mg/m2 on Days 1, 8, and 15 of a 28-day cycle. Therapy continued for up to ten cycles unless disease progression or excessive toxicity mandated discontinuation. RESULTS: With a median relative dose intensity of 96%, toxicity was mild and neutropenia of > or = Grade 3 (according to National Cancer Institute criteria) occurred in 30% of patients, without episodes of febrile neutropenia. One case of hemolytic-uremic syndrome, most likely related to gemcitabine use, was observed. Overall, 2 objective responses were observed (response rate of 7%; 95% confidence interval, 1-24%). The median survival was 8 months. CONCLUSIONS: At the prescribed dosage and schedule, single agent gemcitabine appears to have limited activity in chemotherapy-naive patients with malignant pleural mesothelioma.     

Epirubicin and gemcitabine as first-line treatment in malignant pleural mesothelioma

Malignant pleural mesothelioma represents a rare disease, for which chemotherapy actually remains unsatisfactory. From August 1998 to November 2001, 28 chemo-radio-immunonaive patients were consecutively enrolled in the trial: 22/6 males/females; median age 63 years (range, 45-79); median ECOG PS 1 (range, 0-2). They were treated with epirubicin (100 mg/m2 iv on day 1) plus gemcitabine (1000 mg/m2 iv on days 1 and 8) every 4 weeks for 6 cycles. Patients who responded to chemotherapy (n = 6) were subsequently treated with interleukin-2 (4,500,000 IU) subcutaneously every other day, until progression. A total of 124 epirubicin-gemcitabine cycles were administered (median, 6/patient; range, 2-6). Twenty-six patients were evaluated for toxicity. According to WHO criteria, we observed grade III-IV hematological and gastrointestinal toxicity respectively in 3 patients (11%) and 1 patient (3%). No red cell transfusions were required and no toxic deaths occurred. Two patients (8%) could not be evaluated for response (no therapy performed). According to WHO criteria, the final responses were: partial in 4 patients (14%), stable disease in 19 patients (69%), and progression in 3 patients (10%). In 26 patients, the median survival was 55 weeks (range, 7-222) and median time to progression 30 weeks (range, 4-156). At the time of this writing, no patient is alive. The 1-year survival was 32%, 2-year survival 11%, and 4% at 3 and 4 years. All patients were at stage III, and time to progression was 58 weeks and survival 63.5 weeks, without any toxicity. This multi-center phase II clinical trial showed that epirubicin plus gemcitabine, as a first-line treatment in malignant pleural mesothelioma, has promising activity with a good tolerability profile and symptom palliation. The role of interleukin-2 in maintenance therapy for malignant pleural mesothelioma is encouraging and requires further study.     

Gemcitabine for malignant mesothelioma: A phase II trial by the Cancer and Leukemia Group B

PURPOSE: The CALGB conducted a phase II multicenter trial to evaluate the activity of gemcitabine in malignant mesothelioma (CALGB protocol 9530). PATIENTS AND METHODS: Seventeen patients were accrued between February 1996 and May 1996 and received gemcitabine 1500 mg/m(2) by intravenous infusion over 30 min weekly for 3 weeks, followed by a 1 week break. Eligibility included a performance status of 0-2 by CALGB criteria, and no prior chemotherapy. Nine patients had epithelial cell type and eight had mixed or sarcomatoid cell types. There were 11 cases with measurable disease and six with evaluable disease. RESULTS: There were no complete or partial responders. Eight patients had stable disease, seven developed progressive disease, and two were not evaluable for tumor response. Two patients had minor responses. Median survival from study entry was 4.7 months (95% CI 3.1-12.9 months); one year survival was 24% (95% CI 10-55%). One patient remains alive at 37 months. There were two early deaths, one from disease progression and one from pneumonia. Toxicity was mild and included anemia, lymphopenia and infection; no patient experienced grades three or four thrombocytopenia. CONCLUSION: No antitumor activity was observed for single-agent gemcitabine in patients with malignant mesothelioma in this multicenter phase II study.     

Phase II trial of gemcitabine/irinotecan in refractory or relapsed small-cell lung cancer

BACKGROUND: Gemcitabine and irinotecan have shown a broad range of activity in solid tumors, including small-cell lung cancer (SCLC), with a synergistic effect on SCLC cell lines. The objective of this phase II trial was to evaluate the activity of gemcitabine/irinotecan in patients with relapsed SCLC. PATIENTS AND METHODS: Thirty-five patients (15 with refractory disease and 20 with sensitive disease) who had experienced treatment failure with 1 previous chemotherapy regimen were recruited. Treatment consisted of gemcitabine 1,000 mg/m(2) and irinotecan 100 mg/m(2) on days 1 and 8 of a 21-day cycle for a maximum of 6 cycles. Eligibility criteria included an Eastern Cooperative Oncology Group performance status of 0-2, adequate organ function, and signed informed consent. RESULTS: All 35 patients were assessable for response, survival, and toxicity. Best objective responses exhibited were as follows: complete response in 2 patients (6%), partial response in 4 (11%; 95% confidence interval [CI], 21%-61%), stable disease in 7 (20%; 95% CI, 9%-45%), and progressive disease in 22 (63%; 95% CI, 17%-57%). Median time to disease progression was 3.4 months and median survival was 5.8 months. The 1-year survival rate was 34%. Toxicity was mainly hematologic. Grade 3/4 nausea and vomiting occurred in 9% of patients, neuropathy occurred in 2.8%, and diarrhea occurred in 14.3%. Survival was not significantly different for patients with refractory versus sensitive disease. CONCLUSION: The combination of gemcitabine/irinotecan was shown to be active as second-line chemotherapy, especially in patients with refractory disease.     

Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesothelioma

BACKGROUND: We conducted a phase 2, multicenter, open-label study of erlotinib plus bevacizumab in patients with malignant pleural mesothelioma who had previously received 1 prior chemotherapy regimen. These agents have activity in non-small cell lung cancer, but their role in mesothelioma is unclear. The primary endpoint is response rate. Secondary endpoints include time to progression, survival, and toxicity. METHODS: Eligible patients with mesothelioma who had previously received 1 chemotherapy regimen were treated with erlotinib 150 mg per os daily and bevacizumab 15 mg/kg administered intravenously on Day 1 of a 21-day cycle. Treatment continued until disease progression or development of significant toxicity. Tumor response was assessed after every 2 cycles using previously established mesothelioma response criteria from Byrne and Nowak. RESULTS: Twenty-four eligible patients initiated therapy with erlotinib and bevacizumab between February 2004 and October 2006. There were no complete or partial responses, although 12 patients achieved stable disease for at least 2 cycles of treatment. The median time to progression was 2.2 months (95% confidence interval [CI], 1.4 months-5.9 months). The median survival was 5.8 months (95% CI, 2.8 months-10.1 months). The most common toxicities were rash and diarrhea. There were no treatment-related deaths, intracranial bleeding, or hemoptysis. CONCLUSIONS: The combination of erlotinib and bevacizumab was tolerated reasonably well, but there was no evidence of radiographic response. This study demonstrates the feasibility of conducting trials in mesothelioma patients who have failed first-line therapy. More therapeutic studies with effective agents are needed for these patients.     

Gemcitabine and cisplatin in unresectable malignant mesothelioma of the pleura: a phase II study of the Southwest Oncology Group (SWOG 9810)

PURPOSE: The purpose of this open-label phase II SWOG study was to evaluate the activity of gemcitabine (Gemzar; Eli Lilly, Indiana, USA) and cisplatin combination therapy, in patients with unresectable malignant mesothelioma of the pleura. PATIENTS AND METHODS: Fifty eligible chemotherapy na?ve patients with histologically proven malignant mesothelioma of the pleura, and a SWOG performance status 0-2 were enrolled between February 1999 and August 2000. Treatment consisted of gemcitabine 1000mg/m(2) and cisplatin 30mg/m(2) on days 1, 8 and 15 of a 28-day cycle, until progression of disease or two cycles beyond complete response. RESULTS: Using SWOG response criteria, one patient had a confirmed complete response and five patients had a confirmed partial response, for a total response rate of 12% (95% CI 5-24%). All the responses were seen in patients with epithelioid or unspecified histology. Stable disease was seen in 25 patients (50%). The median overall survival was 10 months (95% CI 7-15 months), with a median progression-free survival of 6 months. Sixteen patients experienced Grade 4 toxicity. Twelve of these Grade 4 toxicities were hematologic. There were no treatment-related deaths. CONCLUSIONS: Cisplatin-gemcitabine combination chemotherapy has modest activity with an acceptable toxicity profile, as first line treatment for patients with malignant mesothelioma.     

An open phase II trial of gemcitabine, oxaliplatin and vinorelbine combination as first-line therapy in advanced non-small cell lung cancer patients

The purpose of this multicentric Phase II study was to evaluate the safety and efficacy of a gemcitabine/oxaliplatin/vinorelbine combination as first-line therapy in advanced non-small cell lung cancer patients. Patients followed a fortnightly drug schedule, receiving on day 1, vinorelbine 25mg/m(2) (20-min infusion); gemcitabine 700 mg/m(2) (70-min infusion, fixed 10mg/m(2)/min); and on day 2, oxaliplatin 85 mg/m(2) (2-h infusion). Thirty-nine patients with a median age of 58 years received a total of 306 cycles (median 8 cycles); 67% were males. Most had adenocarcinoma (51%), large-cell (23%) and squamous cell carcinoma (21%); 15% had stage IIIB and 85% stage IV. There was one complete response (3%; 95% CI: 0.1-13%), 15 partial responses (PR) (38%; 95% CI: 23-55%), and 13 patients with stable disease (33%; 95% CI: 19-50%) of at least 2 months duration, for an overall non-progression rate of 74%. Median progression-free survival (PFS) was 4.1 months (95% CI: 3.1-8.7) and overall survival was 11.7 months (95% CI: 7.7-19.4). No treatment-related deaths occurred and very few grade 3-4 events were observed. Overall, the regimen was well tolerated and the planned recommended dose intensity was safely delivered to more than 95% of patients. This triple combination therapy study yielded favourable efficacy and toxicity results, which merit further evaluation in prospective randomised trials.     

Gefitinib in patients with malignant mesothelioma: a phase II study by the Cancer and Leukemia Group B.

PURPOSE: The Cancer and Leukemia Group B conducted a phase II study of gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, in patients with previously untreated malignant mesothelioma. EXPERIMENTAL DESIGN: Eligible patients had unresectable pleural or peritoneal mesothelioma, measurable disease, no prior therapy, and performance status 0-1 by Cancer and Leukemia Group B criteria. Gefitinib (500 mg p.o.) was administered once a day for 21 days. Patients underwent restaging after every two cycles. Therapy was continued until disease progression or unacceptable toxicity. RESULTS: The most common grade 3 toxicities were diarrhea (16%) and nausea (12%). Of 43 patients enrolled, 1 patient (2%) had a complete response, 1 patient (2%) had a partial response, 21 (49%) had stable disease lasting two to eight cycles, 15 (35%) had progressive disease, and 5 (12%) had early deaths. One-year survival was 32% [95% confidence interval (CI), 21-50%]. Median survival and failure-free survival were 6.8% (95% CI, 3.5-10.3) and 2.6 months (95% CI, 1.5-4.0), respectively. The 3-month failure-free survival was 40% (95% CI, 25-56%). EGFR expression score by immunohistochemistry done in 28 patients was categorized as low (EGFR 1+ or 2+) or high (EGFR 3+) expression: 97% had EGFR overexpression (2+ or 3+). The median and 3-month failure-free survival were 3.6 months and 40% for those patients with low EGFR expression compared with 8.1 and 40% for those with high EGFR expression. CONCLUSIONS: Although 97% of patients with mesothelioma had EGFR overexpression, gefitinib was not active in malignant mesothelioma. EGFR expression does not correlate with failure-free survival.     

Oxaliplatin and raltitrexed in the treatment of inoperable malignant pleural mesothelioma: results of a pilot study

AIMS AND BACKGROUND: The treatment of inoperable malignant pleural mesothelioma is a challenge for the oncologist. Available chemotherapy regimens achieve poor results, therefore new agents or combinations are needed. In a phase I study, the combination of oxaliplatin and raltitrexed was shown to be active against malignant pleural mesothelioma. We herein report the results of a pilot study about the treatment of this disease. METHODS: From April 1999 to June 2000, we enrolled 11 chemotherapy-na?ve patients with inoperable malignant pleural mesothelioma suitable to receive the following combination chemotherapy: raltitrexed, 3 mg/m2 iv, and oxaliplatin, 130 mg/m2, as a 2-hr infusion every 3 weeks. RESULTS: Four partial responses, 1 regression of disease (objective response rate, 45%; 95% CI, 15.6-74.4%), 4 stable diseases and 2 progressions of disease were observed. An improvement in disease-related symptoms was recorded in all responders and in 2 patients with stable disease. Toxicity was mild, with no toxic-related death and only 1 episode of grade 4 neurotoxicity. CONCLUSIONS: We consider the combination promising and worthy of further studies.     

Gemcitabine and vinorelbine in pemetrexed-pretreated patients with malignant pleural mesothelioma

BACKGROUND: Pemetrexed-cisplatin chemotherapy is the standard of care in the first-line treatment of unresectable malignant pleural mesothelioma (MPM). Second-line cytotoxic therapy is considered for a growing group of patients, but the optimal treatment has not been defined to date. Gemcitabine and vinorelbine have shown activity in the first-line setting. The objective of this study was to evaluate the activity and toxicity of the gemcitabine-vinorelbine combination in pemetrexed-pretreated patients with MPM. METHODS: From January 2004 to September 2006, 30 consecutive patients who were pretreated with pemetrexed with or without a platinum-derivative were enrolled. Gemcitabine 1000 mg/m(2) and vinorelbine 25 mg/m(2) were administered intravenously on Days 1 and 8 every 3 weeks. Treatment was repeated for a maximum of 6 cycles or until progression or unacceptable toxicity. RESULTS: A partial response was observed in 3 patients (10%; 95% confidence interval [CI], 2.1-26.5%), and 10 patients (33.3%; 95% CI, 17.3-52.8%) had stable disease after treatment. Overall, 13 patients (43.3%; 95% CI, 25.5-62.6%) achieved disease control. The median time to progression was 2.8 months (range, 0.6-12.1 months), and the median survival was 10.9 months (range, 0.8-25.3 months). Hematologic toxicity was acceptable, with grade 3 or 4 neutropenia occurring in 11% of patients and thrombocytopenia occurring in 4% of patients; no case of febrile neutropenia was observed. Nonhematologic toxicity generally was mild. CONCLUSIONS: The gemcitabine and vinorelbine combination was moderately active and had an acceptable toxicity profile in pemetrexed-pretreated patients with MPM. The role of second-line treatment in MPM needs to be evaluated in prospective trials in large series of patients who are stratified according to previous treatment and prognostic factors.     

Combination chemotherapy with mitoxantrone, methotrexate, and mitomycin (MMM regimen) in malignant pleural mesothelioma: a phase II study

The prognosis of malignant pleural mesothelioma is poor, with a median survival time from diagnosis of 7 to 17 months. At present there is no standardized treatment of this neoplasia. Between July 1995 and January 1999, 22 patients with malignant pleural mesothelioma were enrolled in our study. The characteristics of patients were: 16 men and 6 women; median age 61 years (range, 49-77 years); stage (according to Butchart): 8 patients stage I, 10 stage II, 2 stage III, and 2 stage IV; cytologic diagnosis in 5 cases and histologic diagnosis in 17 cases. The treatment consisted of mitoxantrone 10 mg/m2 intravenous (IV) or intrapleural (IPL), methotrexate 35 mg/m2 IV, and mitomycin 7 mg/m2 IV on day 1 and repeated every 3 weeks, with mitomycin in alternate cycles (MMM regimen). One complete response (4.5%) (42 months of duration) and 6 partial responses (27.3%) (5, 5, 7, 9, 14, and 19 months of duration) were achieved; the overall response rate (ORR) was 31.8% (95% CI, 12.4-51.3%); 7 patients were stable under this treatment (31.8%). According to the pathologic type, ORR for the only epithelial type was 39.9% (95% CI, 15.2-64.8%). Median time to progression was 6 months (range, 1-22). The overall median survival time was 13.5 months (range, 1-50); the median survival time of responders significantly differed from that of nonresponders (18.0 versus 8.5 months; p = 0.017). This treatment produced a considerable clinical benefit, with improvement of dyspnea (68.4%) and pain (33.3%); 15 of 19 patients (78.9%) with pleural effusion at the time of diagnosis showed an important reduction in pleural fluid during chemotherapy. Hematologic toxicity was the main side effect; World Health Organization grade III to IV of neutropenia, anemia, and thrombocytopenia were observed in 81.8%, 13.6%, and 22.7% of patients, respectively. From the data presented here, this regimen can be considered active in the treatment of malignant pleural mesothelioma.     

Carboplatin and pemetrexed in the management of malignant pleural mesothelioma: a realistic treatment option?

BACKGROUND: Malignant pleural mesothelioma is an aggressive cancer. Chemotherapy with cisplatin and pemetrexed can improve overall survival but has a toxic profile. Substitution of cisplatin with carboplatin may avoid some potential side-effects. Therefore, we undertook a retrospective review to assess the effectiveness and tolerability of carboplatin and pemetrexed in patients with malignant pleural mesothelioma in clinical practice. METHODS: Patients with malignant pleural mesothelioma who had been treated with carboplatin and pemetrexed were retrospectively identified from pharmacy databases. The endpoints were disease control rate, time to treatment failure, clinical improvement rate and overall survival. We also evaluated any significant haematological and non-haematological toxicities. RESULTS: A total of 49 patients were identified. Of 45 evaluable cases, the disease control rate was achieved in 34 patients (69%, 95% CI 55-82, intention to treat analysis). The clinical response rate was achieved in 34 out of 49 patients (69%, 95% CI 55-82). The median time to treatment failure was 4.6 months (95% CI 3.4-5.8) and median overall survival was 14 months (95% CI 9.5-18.5). Grade 3/4 haematological toxicities were observed in 7 patients (14.3%). Grade 3/4 non-haematological toxicities were seen in 12 patients (24.5%). No toxic deaths were recorded. CONCLUSION: The combination of carboplatin and pemetrexed may be a viable option in the treatment of malignant pleural mesothelioma.     

Phase II trial of carboplatin, gemcitabine, and capecitabine in patients with carcinoma of unknown primary site

BACKGROUND: The purposes of this study were to evaluate efficacy and toxicity of the combination of carboplatin, gemcitabine, and capecitabine in patients with carcinoma of unknown primary site (CUP). METHODS: Patients with CUP received carboplatin AUC 5 mg/mL a minute intravenously Day 1, gemcitabine 1000 mg/m(2) intravenously Days 1 and 8, and capecitabine 1600 mg/m(2) orally in divided doses, Days 1-14 of a 21-day cycle for up to 8 cycles. The primary endpoint of the study was objective response rate by intent-to-treat analysis. RESULTS: Thirty-three patients were treated (median age, 58 years; men:women ratio, 19:14). Most patients had a baseline performance status of 1. The objective response rate was 39.4% (95% CI, 22.9%-57.9%) in all patients, 36.4% in 22 patients with well to moderately differentiated adenocarcinoma, and 40.0% in 20 patients with liver metastases. Median progression-free survival time was 6.2 months (95% CI, 5.4%-8.0%), and median survival time was 7.6 months (95% CI, 6.3-14.1). One and 2-year survival rates were 35.6% and 14.2%, respectively. The most frequent grade > or =3 adverse events were neutropenia (67%), thrombocytopenia (48%), and anemia (33%). CONCLUSIONS: The combination of carboplatin, gemcitabine, and capecitabine is active in CUP, especially in patients with liver metastases. This regimen may be a potential therapy for CUP patients with good performance status, particularly those with a suspected origin below the diaphragm.     

Cisplatin and gemcitabine in malignant pleural mesothelioma: a phase II study

Aims of this study were to evaluate the activity and toxicity of gemcitabine and cisplatin combination in malignant pleural mesothelioma (MPM). Patients with histologically proven MPM, < 75 years of age, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2, and measurable MPM were eligible. Patients received gemcitabine 1250 mg/m intravenously on days 1 and 8 and cisplatin 75 mg/m on day 2, every 21 days, for a maximum of 6 cycles. From May 1999 to May 2001, 35 chemonaive patients (median age, 61 years) were enrolled. A total of 177 cycles were administered (median 5 cycles; range 1 to 6). One patient was not evaluable for response and toxicity. Nine (26%) patients had partial responses, 11 (32%) patients had progressive disease, and 14 (41%) stable disease. Median survival for all patients was 13 months. Median progression-free survival was 8 months. Grade 3 (World Health Organization) nausea and vomiting occurred in 35% of patients. Grade 3/4 anemia, grade 3/4 thrombocythemia, and grade 3/4 neutropenia were assessed in 24%, 52%, and 61% of patients, respectively. All other side effects were mild. In conclusion, gemcitabine-cisplatin combination seems to be moderately active in MPM. Furthermore, at this dose and schedule, the toxicity profile could be acceptable.     

First line chemotherapy with planned sequential administration of gemcitabine followed by docetaxel in elderly advanced non-small-cell lung cancer patients: a multicenter phase II study

This multicenter phase II study evaluated, in chemonaive patients with stage IIIB-IV NSCLC, age >or=70 and with a performance status 0-2, the activity, efficacy and tolerability of planned sequential administration of gemcitabine 1200 mg m(-2) on days 1 and 8 every 3 weeks for three courses followed by three cycles of docetaxel 37.5 mg m(-2) on days 1 and 8 every 3 weeks, provided there was no evidence of disease progression. A total of 56 patients entered the study. According to intention-to-treat analysis, the objective response rate was 16.0% (95% CI 7.6-28.3%); 23 patients (41.0%) had stable disease and 24 patients (43%) had progressive disease. Five patients who had a stable disease after three courses of gemcitabine obtained a conversion to partial response by docetaxel. Median time to progression was 4.8 months (95% CI 3.6-6.0 months) and median duration of survival was 8.0 months (95% CI 5.6-10.5 months). The 1-year survival rate was 34%. No grade 4 haematological toxicity was observed and grade 3 neutropenia and thrombocytopenia were reported in 5.4 and 3.6% of the patients, respectively. Grade 3/4 mucositis and grade 3 diarrhoea, both occurred in 3.6% of the patients and grade 3 asthenia was observed in 9% of patients. One patient reported a grade 4 skin toxicity. No treatment-related deaths occurred. Sequential gemcitabine and docetaxel is a well-tolerated and effective regimen in elderly advanced NSCLC patients.