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PROTOCOL ABSTRACT
PROTOCOL:
Phase II study of induction therapy with intrapleural liposomal entrapped cisplatin analog (L-NDDP) followed by surgical resection and post-operative radiotherapy in patients with malignant pleural mesothelioma
| STUDY CHAIRMAN: | Dong Moon Shin, MD | ||
| Department of Thoracic/Head & Neck Medical Oncology |
Phone 713-792-6363 |
Box 80 |
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| STUDY CO-CHAIRMAN: | Craig Stevens, MD, PhD Roy Smythe, MD |
OBJECTIVES:
- To determine the pathologic response rate treated with L-NDDP intrapleurally as an induction therapy for patients with malignant pleural mesothelioma.
- To determine the surgical resectability, progression free survival, and overall survival of patients with malignant pleural mesothelioma treated with intrapleural L-NDDP for an induction regimen, and followed by surgical resection and post-operative radiotherapy.
- To evaluate the toxicity of intrapleural L-NDDP, and the toxicity of combined approaches with surgery and radiotherapy.
RATIONALE:
There is no standard treatment for patients with malignant pleural mesothelioma
(MPM). Aggressive phase II studies of surgical resection followed by systemic
chemotherapy have been resulted in poor outcome with high rate of recurrent
disease.
We are currently conducting a prospective phase II study in patients with
MPM who had free flowing pleural effusion. The starting dose was NDDP
450 mg/m2 and liposome 6750 mg/m2 in a volume of 225 ml/m2. L-NDDP was
given through a Tenkoff catheter one week after the first thoracoscopy
and treated every 3 to 4 weeks thereafter. Among 9 evaluable patients
with pathologic examination in post-treated samples, 5 of 9 (56%) patients
whose biopsied tissue samples did not show any viable tumors and 6 of
9 (67%) cytologic specimens showed completely negative in microscopic
examination. No hematologic side effects were observed. These preliminary
results suggest that intrapleural L-NDDP treatment yields a high rate
of pathologic response, and is a promising approach to therapy for patients
with MPM.
We propose now a phase II study of induction therapy with L-NDDP followed
by surgical resection and post-operative radiotherapy in patients with
MPM to determine the pathologic response rate, surgical resectability,
the progression free survival and overall survival rates, and toxicity
evaluation.
ELIGIBILITY: (List Major Criteria)
- Histologically proven malignant pleural mesothelioma.
- Patients must have free-flowing pleural effusion.
- Patients must not have surgical resection except open biopsy for diagnosis.
- Patients must not have radiotherapy.
- Patients with prior pleurothesis on the same side of MPM are eligible as long as they have a free-flowing pleural effusion.
- Patients must a life expectancy of at least 12 weeks and a Zubrod's performance scale of £ 2.
- Patients must be ³ 18 years of age.
- Patients must have adequate bone marrow function (WBC ³ 4,000/mm3; platelet ³ 100,000/mm3), renal function (creatinine £ 1.5 mg%), and hepatic function (total bilirubin < 1.5 mg%; SGPT £ 1.5 times the upper normal limit).
- Patients must sign an informed consent indicating that they are aware of the investigational nature of the study.