Platinum-based doublet chemotherapy in pre-treated malignant pleural mesothelioma (MPM) patients: a mono-institutional experience

Lung Cancer. 2011 Sep;73(3):351-5. doi: 10.1016/j.lungcan.2011.01.005. Epub 2011 Feb 5.

Abstract

Background: The major clinical problems of MPM management are the short duration of response and the early relapse. Currently, after the first-line standard pemetrexed/platinum combination there is not a defined regimen for the second line treatment of MPM, and the clinical benefits in fit patients are uncertain. We analyzed the feasibility of gemcitabine/platinum chemotherapy in pretreated MPM patients.

Methods: Eligible patients should have relapsed after first-line chemotherapy with pemetrexed plus cisplatin (24%) or carboplatin (76%); 53% of the patients had previously received trimodality treatment, 18% neoadjuvant chemotherapy followed by pleurectomy/decortication, 29% were inoperable. Patients had to have PS=0-2, adequate organ function, measurable disease. Chemotherapy was gemcitabine 1000 mg/m(2) days 1, 8 associated to the alternative platinum compound respect to 1st line, i.e. cisplatin 75 mg/m(2) or carboplatin AUC 5 day 1 every 3 weeks, for 3-6 cycles. Baseline staging and reassessment after cycles 3 and 6 were performed with CT-scan.

Results: Since 2006 17 relapsed MPM patients were referred to our centre. Patients were 12 males and 5 females; median age: 61 years (range 47-74); histology: 12 epithelial, 4 sarcomatoid and 1 biphasic. PS 1-2 (15:2). The combination of gemcitabine with carboplatin/cisplatin was administered as second line treatment in 13 (76%) patients, as third line in 4 (24%) patients. Two patients were lost to follow-up without re-evaluation, therefore radiologic and clinical response was assessable in 15 (88%) patients. Among evaluable patients 10 (67%) showed stable disease and 5 (33%) progressive disease. Symptoms improved in 8 (53%) cases. In the intent-to-treat population median survival was 28 weeks (range 13-168) and median time-to-treatment failure 15 weeks (range 3-75). Toxicity profile showed 2 (13%) grade 4 and 6 (40%) grade 3 thrombocytopenia, 4 (27%) grade 3 leucopenia, 3 (20%) grade 3 anaemia and 6 (40%) of grade 3 neutropenia. Grade 3 non haematological toxicities were nausea (14%) and asthenia (21%).

Conclusion: Gemcitabine-platinum regimens are able to control symptoms and disease progression with a modest toxicity profile. The present results from a small series of patients should be confirmed by a prospective trial in a larger cohort of patients.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / therapeutic use
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Disease Progression
  • Drug Resistance
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Glutamates / administration & dosage
  • Glutamates / adverse effects
  • Guanine / administration & dosage
  • Guanine / adverse effects
  • Guanine / analogs & derivatives
  • Humans
  • Leukopenia / etiology
  • Male
  • Mesothelioma / drug therapy*
  • Mesothelioma / pathology
  • Mesothelioma / physiopathology
  • Mesothelioma / surgery
  • Middle Aged
  • Neoplasm Staging
  • Pemetrexed
  • Platinum Compounds / administration & dosage
  • Platinum Compounds / adverse effects
  • Pleural Neoplasms / drug therapy*
  • Pleural Neoplasms / pathology
  • Pleural Neoplasms / physiopathology
  • Pleural Neoplasms / surgery
  • Thrombocytopenia / etiology

Substances

  • Glutamates
  • Platinum Compounds
  • Pemetrexed
  • Deoxycytidine
  • Guanine
  • Carboplatin
  • Gemcitabine