A phase I trial of the oral platinum analogue JM216 with concomitant radiotherapy in advanced malignancies of the chest

JM216 is an orally administered platinum analogue. We undertook this study to determine the maximally tolerated dose (MTD) of JM216 when administered with concomitant radiotherapy to the chest (200 cGy daily, 5x/week) in pati ents with locoregionally advanced non-small cell lung (NSCLC) or esophageal cancer. Patients were excluded for inadequate bone marrow reserve, prior r adiotherapy to the primary tumor or previous treatment with platinum drugs. A dose-limiting toxicity (DLT) was defined using the National Cancer Insti tute (NCI) Common Toxicity Criteria (CTC) and consisted of grade greater th an or equal to2 renal, hepatic, cardiac, or pulmonary toxicity or grade gre ater than or equal to3 hematologic, neurological, or gastrointestinal toxic ity. A total of 23 patients were registered; two never received treatment a nd are excluded from analyses. Six patients were treated at a dose of 30 mg /m(2)/day for 5 days with two grade 2 DLT's: cough (1 pt) and elevated tran s-aminases (1 pt). Seven evaluable patients were treated at 60 mg/m(2)/day and seven experienced grade 3 or 4 toxicity, five related to myelosuppressi on. The dose was then reduced to 45 mg/m(2)/d. Eight patients were evaluabl e for toxicity, of which 5 experienced DLT: myelosuppression (3 pts), esoph agitis (2 pts), dyspnea (1 pt), and elevated creatinine (1 pt). Fourteen pa tients were evaluable for efficacy, of which 6 had an objective response, i ncluding one complete response. The recommended phase II dose of JM216 with concurrent radiation therapy is 30 mg/m(2)/d for 5 days. The major DLT is myelosuppression with only limited increased toxicity within the field of r adiation. This conceivably may limit the use of JM216 as a radiation sensit izer.