Trial Information

Aggressive Multi-Modality Management of Malignant Pleural Mesothelioma

OBJECTIVES:

Primary

- Assess the response to induction combination chemotherapy comprising methotrexate,
vinorelbine ditartrate, and cisplatin in patients with previously untreated malignant
pleural mesothelioma.

Secondary

- Assess the tolerability and toxicity of this regimen in these patients.

- Determine relapse-free and overall survival of patients treated with induction
combination chemotherapy with or without surgery and hemithoracic radiation.

- Assess the impact of induction combination chemotherapy on operability and surgical
success.

- Evaluate the impact of these treatment regimens on quality of life.

OUTLINE:

- Induction chemotherapy: Patients receive MVP chemotherapy comprising cisplatin IV over
30-60 minutes on day 1 and vinorelbine ditartrate IV over 5-10 minutes and methotrexate
IV over 5-30 minutes on days 8, 15, and 22. Treatment repeats every 28 days for 2
courses. Patients with unresectable disease may receive up to 2 additional courses of
induction chemotherapy. Patients requiring palliative radiotherapy or who have
progressive disease are removed from the study. Patients with resectable disease or
sarcomatoid histology and T1-3, N1-2 disease with a complete or partial response to
induction chemotherapy proceed to surgery.

- Surgery: Patients with extensive disease undergo palliative debulking pleurectomy and
decortication and then are taken off study. All other patients undergo a thoracotomy
with an extrapleural pneumonectomy and then proceed to chemoradiotherapy.

- Chemoradiotherapy: Beginning 6-10 weeks after surgery, patients undergo 3-dimensional
conformal or intensity-modulated radiotherapy once daily, 5 days a week, for 6 weeks.
Patients also receive cisplatin IV over 30-60 minutes on days 1 and 22. Patients with
responding disease proceed to adjuvant chemotherapy.

- Adjuvant chemotherapy: Patients receive 2 additional courses of MVP chemotherapy as
above.

Quality of life is assessed at baseline, after each course of induction chemotherapy, before
surgery, and then every 3 months thereafter.

After completion of study therapy, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 36 patients will be accrued for this study.