A Phase II Trial Of Pemetrexed In Malignant Pleural Mesothelioma (MPM) Patients: Clinical Outcome, Role Of Vitamin Station, Respiratory Symptoms Upplemenand Lung Function

Reviewer: Heather Jones, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 22, 2002

Presenter: Dong M Shin,
Presenter's Affiliation: University of Pittsburgh
Type of Session: Scientific


    Malignant pleural mesothelia (MPM) is generally caused by exposure to asbestos and is commonly accompanied by pleural effusion, sometimes making radiologic images difficult to interpret. As the worldwide incidence of MPM increases, few chemotherapeutic agents have demonstrated more than modest activity. Pemetrexed, a novel multi-targeted antifolate that inhibits thymidylate synthase and other folate-dependent enzymes, has been demonstrated to have activity in a wide variety of tumors. Supplementation of folate and vitamin B12 has been shown to reduce toxicity associated with pemetrexed. The objective of this phase II study of pemetrexed in patients with advanced MPM included evaluating tumor respone rate (RR), time to progression (TTP) median survival (MS), and toxicity.

Materials and Methods

  • 64 chemotherapy-naive patients received pemetrexed, 500 mg/m2 (10 min IV infusion day 1) every 21 days
  • Low-dose folic acid (FA) and vitamin B12 (B12) were added during the study as this has been shown to reduce grade (G) 3/4 toxicities
  • 43 patients were fully supplemented (received FA/B12 throughout)
  • 21 patients were non-supplemented (never received FA/B12 )


  • Fully supplemented patients completed a median of 6 cycles; RR:16%; median TTP:4.8 months (mos); MS:13 mos.
  • Non-supplemented patients completed a median of 2 cycles; RR: 9.5 %; median TTP:3 mos; MS: 8 mos. G3/4 hematological toxicities for fully supplemented group were neutropenia (4.7/4.7%), leukopenia (9.3/0%), thrombocytopenia (2.3/0%), respectively compared to non-supplemented patients - neutropenia (14.3/ 38.1 %), leukopenia (28.6/9.5 %) and thrombocytopenia (1.6/1.6 %)
  • No significant non-hematological toxicities were reported
  • On the Lung Cancer Symptom Scale pt scale, responders noted improvement in anorexia, fatigue, dyspnea, pain, symptom distress, activity level and global QoL.
  • On the LCSS observer scale, 63% of responders were rated as improved in total score.
  • Patients who responded to treatment showed an increase in lung volume and motility.

Author's Conclusions

    This study demonstrates promising activity and good tolerability of pemetrexed in patients with mesothelioma. Vitamin supplementation resulted in a marked decrease in the amount of grade 3/4 hematologic toxicity without reducing the clinical efficacy of pemetrexed.

Clinical/Scientific Implications

    Despite many trials with numerous regimens, none of these combination chemotherapy regimens have consistently yielded response rates higher than those seen in single-agent studies. The development and testing of newer agents for the treatment of malignant pleural mesothelia are clearly needed. These are early results, yet the responses and dramatic reduction of toxicity in the patients receiving ALIMTA and folic acid are encouraging. Future clinical trials should be carried out to define the role that this drug will play in the treatment of malignant pleural mesothelia.

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