A Phase I Trial of the Oral Platinum Analogue JM216with Concomitant Radiotherapy in Advanced Malignancies of theChest

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• 作者：George ; Christopher M. ; Haraf ; Dan J. ; Mauer ; Ann M. ; Krauss ; Stuart A. ; Hoffman ; Philip C. ; Rudin ; Charles M. ; Szeto ; Livia ; Vokes ; Everett E.
• 关键词：JM216 ; radiation therapy ; chemotherapy ; phase I ; non ; small cell lung cancer
• 刊名：Investigational New Drugs
• 出版年：2001
• 出版时间：2001
• 年：2001
• 卷：19
• 期：4
• 页码：303-310
• 全文大小：83 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Pharmacology and Toxicology
  
• 出版者：Springer Netherlands
• ISSN：1573-0646

文摘

JM216 is an orally administered platinumanalogue. We undertook this study todetermine the maximally tolerated dose(MTD) of JM216 when administered withconcomitant radiotherapy to the chest(200 cGy daily, 5×/week) in patients withlocoregionally advanced non-small cell lung(NSCLC) or esophageal cancer. Patientswere excluded for inadequate bone marrowreserve, prior radiotherapy to the primarytumor or previous treatment with platinumdrugs. A dose-limiting toxicity (DLT) wasdefined using the National Cancer Institute(NCI) Common Toxicity Criteria (CTC) andconsisted of grade ≥2 renal, hepatic,cardiac, or pulmonary toxicity or grade ≥3hematologic, neurological, orgastrointestinal toxicity. A total of 23patients were registered; two neverreceived treatment and are excluded fromanalyses. Six patients were treated at adose of 30 mg/m²/day for 5 days withtwo grade 2 DLT's: cough (1 pt) andelevated trans-aminases (1 pt). Sevenevaluable patients were treated at60 mg/m²/day and seven experiencedgrade 3 or 4 toxicity, five related tomyelosuppression. The dose was thenreduced to 45 mg/m²/d. Eight patientswere evaluable for toxicity, of which 5experienced DLT: myelosuppression (3 pts),esophagitis (2 pts), dyspnea (1 pt), andelevated creatinine (1 pt). Fourteenpatients were evaluable for efficacy, ofwhich 6 had an objective response,including one complete response. Therecommended phase II dose of JM216 withconcurrent radiation therapy is30 mg/m²/d for 5 days. The major DLTis myelosuppression with only limitedincreased toxicity within the field ofradiation. This conceivably may limit theuse of JM216 as a radiation sensitizer.