Cisplatin and Gemcitabine in Malignant Pleural Mesothelioma: A Phase II Study

Abstract

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.

Multicenter, Double-Blind, Placebo-Controlled, Randomized Phase II Trial of Gemcitabine/Cisplatin Plus Bevacizumab or Placebo in Patients With Malignant Mesothelioma

“…1 In a malignancy with three major pathologic subtypes (epithelial, sarcomatoid, and biphasic), four sites of disease origin (pleura, peritoneum, pericardium, and tunica vaginalis), and several other key prognostic factors that can substantially affect outcomes, 27,28 it should not be surprising that six small phase II trials evaluating the gemcitabine/cisplatin combination in MM produced widely discordant results. [5][6][7][8][9][10] Therefore, to discern the impact of the addition of a novel agent to this chemotherapy backbone, we designed what we believe is the first randomized phase II trial ever performed in patients with MM. It demonstrates that the addition of bevacizumab to gemcitabine/cisplatin does not improve PFS in this disease.…”

“…This study also confirms the data from prior investigators regarding the significant activity of the gemcitabine/cisplatin combination in patients with MM. [3][4][5][6][7][8][9][10] The addition of bevacizumab to chemotherapy improves outcomes in cancers of the breast, colon, lung, and kidney. [32][33][34][35] Given preclinical data that supported a key role for the VEGF pathway in MM biology [12][13][14] and the multiple phase II trials that suggested modest activity for other VEGF inhibitors in patients with MM, 11,[15][16][17][18][19][20] it was plausible to assume that adding bevacizumab to systemic chemotherapy in patients with MM would replicate the results observed in these other cancers.…”

Chemotherapy treatment in malignant pleural mesothelioma: a difficult history

“…The combination of cisplatin plus gemcitabine was also evaluated in some phase II trials suggesting that it may be an alternative in patients not candidates to pemetrexed, despite heterogeneity between studies with response rates and survival ranging from 12-48% and 9.5-12 months, respectively (3,(27)(28)(29)(30)(31). Furthermore, the use of carboplatin with gemcitabine has been investigated showing good tolerance and a response rate of 26% (32).…”

Neoadjuvant Chemotherapy in Malignant Pleural Mesothelioma

“…On the basis of results in the metastatic disease, the association of carboplatin or cisplatin plus gemcitabine was considered as an effective treatment (Byrne et al,1999;Nowak et al, 2002;Favaretto et al, 2003;Castagneto et al, 2005;Kalmadi et al, 2008).…”