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Investigational New Drugs

, Volume 19, Issue 4, pp 303–310 | Cite as

A Phase I Trial of the Oral Platinum Analogue JM216 with Concomitant Radiotherapy in Advanced Malignancies of the Chest

  • Christopher M. George
  • Dan J. Haraf
  • Ann M. Mauer
  • Stuart A. Krauss
  • Philip C. Hoffman
  • Charles M. Rudin
  • Livia Szeto
  • Everett E. Vokes
Article

Abstract

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.

JM216 radiation therapy chemotherapy phase I non-small cell lung cancer 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Christopher M. George
    • 1
  • Dan J. Haraf
    • 2
    • 3
  • Ann M. Mauer
    • 1
    • 3
  • Stuart A. Krauss
    • 1
  • Philip C. Hoffman
    • 1
  • Charles M. Rudin
    • 1
    • 3
  • Livia Szeto
    • 1
  • Everett E. Vokes
    • 1
    • 2
    • 3
  1. 1.Section of Hematology/OncologyUniversity of Chicago
  2. 2.Section of Radiation & Cellular OncologyUniversity of ChicagoU.S.A.
  3. 3.Cancer Research CenterUniversity of ChicagoChicagoU.S.A.

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