Pemextred and cisplatin vs. cisplatin alone in chemonaive patients with malignant pleural mesothelioma.

This new treatment is now standard for Malignant Pleural Mesothelioma. It has proven to improve both breathlessness and pain. Data presented at ESMO included the involvement of a supplement for Vitamin B12 and Folinic Acid which is now standard treatment for MPM.

No approved or effective chemotherapy has been identified for malignant pleural mesothelioma (MPM).

In a phase I trial of cisplatin and pemextred, a novel antifolate targeting key enzymes in purine and pyrimidine synthesis, promising antitumour activity was observed in MPM patients (pts). As a result, a randomised single-blind phase III trial was designed, with survival as primary endpoint.

Arm A consisted of pemextred 500mg/m2 IV followed by cisplatin 75mg/m2 on D1 q3 weeks.

Arm B consisted of cisplatin 75 mg/m2 alone on D1 q3 weeks.

After 118 pts had enrolled, an unacceptable rate of severe toxicity including drug-related deaths occurred in Arm A. To improve the safety profile and to maintain blinding, all subsequent pts in both the arms received low dose folic acid and vitamin B12 (FA/B12). In total, 456 pts were randomised, 228/Arm A and 228 Arm B form 5/99 to 3/01. Of these, 170 pts in Arm A and 168 pts in Arm B were randomised after required FA/B12 supplementation.

At the time of final analysis, median follow-up was 9.3 months with 304 of 448 possible deaths having occurred. Pts in Arm A had a longer median survival (MS) (longrank p=0.020), longer time to progressive diseases (TTPD) (longrank p=0.001), and higher response rate (Fishers Exact P<0.001) compared to Arm B. For all patients in Arm A and B, MS was 12.1 and 9.3 months respectively. For FA/B12 supplemented pts in Arm A and B, MS was 13.3 and 10.0 months respectively. For no FA/B12 pts in Arm A and B, MS was 9.5 and 7.2 months respectively. Pts in Arm A had more toxicity including G3/4 neutropenia (ANC), and stomatits than in Arm B. However FA/B12 clearly reduced the frequency of toxicity in Arm A without adversely affecting efficacy. Quality of life and pulmonary function tests were evaluated in this study. The Lung Cancer Symptom Scale components of dyspnea (p=0.004) and pain (p=0.017) were significantly improved in Arm A compared to Arm B at cycle 6. Lung function also improved significantly for Arm A as measured by vital capacity (p=0.006) and forced expiratory volume (FEV1) (p<0.001) at cycle 6. Pemetrexed and cisplatin supplemented with FA/B12 should now be considered standard treatment for patients with non-resectable MPM. For more information on pemextred and cisplatin, please go to the treatment section of virtual cancer centre. For more information on Mesothelioma, please go to the disease section.