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, 5×/week) in patients with locoregionally advanced non-small cell lung (NSCLC) or esophageal cancer. Patients were excluded for inadequate bone marrow reserve, prior radiotherapy to the primary tumor or previous treatment with platinum drugs. A dose-limiting toxicity (DLT) was defined using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) and consisted of grade ≥2 renal, hepatic, cardiac, or pulmonary toxicity or grade ≥3 hematologic, neurological, or gastrointestinal toxicity. A total of 23 patients were registered; two never received treatment and are excluded from analyses. Six patients were treated at a dose of 30 mg/m²/day for 5 days with two grade 2 DLT's: cough (1 pt) and elevated trans-aminases (1 pt). Seven evaluable patients were treated at 60 mg/m²/day and seven experienced grade 3 or 4 toxicity, five related to myelosuppression. The dose was then reduced to 45 mg/m²/d. Eight patients were evaluable for toxicity, of which 5 experienced DLT: myelosuppression (3 pts), esophagitis (2 pts), dyspnea (1 pt), and elevated creatinine (1 pt). Fourteen patients were evaluable for efficacy, of which 6 had an objective response, including one complete response. The recommended phase II dose of JM216 with concurrent radiation therapy is 30 mg/m²/d for 5 days. The major DLT is myelosuppression with only limited increased toxicity within the field of radiation. This conceivably may limit the use of JM216 as a radiation sensitizer.