Abstract
This phase I study wasconducted to determine the dose limitingtoxicity, maximum tolerated doses, andrecommended phase II doses of thecombination of JM-216 and paclitaxel. Patients received paclitaxel intravenouslyover one hour on day 1 of each cycle. OralJM-216 was administered on days 1–5starting after the paclitaxel infusion. Cycles were repeated every 21 days. Patients were accrued at nine differentdosing combinations. JM-216 doses rangedfrom 10–80 mg/m2/day and werecombined with paclitaxel doses of 150, 175,or 200 mg/m2. Forty-three patientswere treated with 146 cycles of therapy. Dose-limiting toxicity, consisting offebrile neutropenia and grade 3thrombocytopenia, was encountered in 2patients at the seventh dose level (JM-21680 mg/m2/day + paclitaxel175 mg/m2). Two intermediate doselevels were explored. The first level(JM-216 70 mg/m2/day + paclitaxel175 mg/m2) produced dose-limitingthrombocytopenia in 1 of 6 patients. However, two additional patients alsodemonstrated delayed recovery fromthrombocytopenia following treatment. As aresult, a second intermediate dose level(JM-216 60 mg/m2/day + paclitaxel200 mg/m2) was filled with sixpatients. No dose-limiting toxicities werereported in any patients at this doselevel. The combination of oral JM-216 andpaclitaxel is well-tolerated with minimalnon-hematologic and reversible hematologictoxicity. The recommended dose for phaseII study is JM-216 60 mg/m2/day for 5days and paclitaxel 200 mg/m2 on day 1repeated every 21 days. Higher doses ofJM-216 are associated with more severethrombocytopenia and delayed hematologicrecovery resulting in subsequent dosingdelays.
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References
BMS-182751 (JM-216). Bristol-Myers Squibb Investigator Brochure, 1994
McKeage MJ, Raynaud F, Ward J, Berry C, O'Dell D, Kelland LR, Murrer B, Santabarbara P, Harrap KR, Judson LR: Phase I and pharmacokinetic study of an oral platinum complex given daily for 5 days in patients with cancer. J Clin Oncol 15: 2691–2700, 1997
Beale P, Raynaud F, Hanwell J, Berry C, Moore S, Odell D, Judson I: Phase I study of oral JM216 given twice daily. Cancer Chemother Pharmacol 42: 142–148, 1998
Fokkema E, Groen HJM, Bauer J, Uges DR, Weil C, Smith IE: Phase II study of oral platinum drug JM216 as first-line treatement in patients with small cell lung cancer. J Clin Oncol 17: 3822–3827, 1999
Greco FA, Thomas M, Hainsworth JD: One-hour paclitaxel infusions: review of safety and efficacy. Cancer J Sci Am 5: 179–191, 1999
Langer CJ, Leighton JC, Comis RL, O'Dwyer PJ, McAleer CA, Bonjo CA, Engstrom PF, Litwin S, Ozols RF: Paclitaxel and carboplatin in combination in the treatment of advanced non-small cell lung cancer (NSCLC): a phase II toxicity, response, and survival analysis (FCCC 93-024). J Clin Oncol 13: 1860–1870, 1995
Hainsworth JD, Urba WJ, Hon JK, Thompson KA, Stagg MP, Hopkins LG, Thomas M, Greco FA: One-hour paclitaxel plus carboplatin in the treatment of advanced non-small cell lung cancer: results of a multicentre, phase II trial. Eur J Cancer 34: 654–658, 1998
Bonomi P, Kim K, Chang A, Johnson D: Phase III trial comparing etoposide (E) cisplatin (C) versus taxol (T) with cisplatin-G-CSF(G) versus taxol-cisplatin in advanced non-small cell lung cancer. An Eastern Cooperative Oncology Group (ECOG) trial. Proc Am Soc Clin Oncol 15: 382, 1996 (abstract 1145)
McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M: Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 334: 1–6, 1996
Ozols RF, Bundy BN, Fowler J, Clarke-Pearson D, Mannel R, Hartenbach EM, Baergen R: Randomized phase III study of cisplatin (CIS)/paclitaxel (PAC) versus carboplatin (CARBO)/PAC in optimal stage III epithelial ovarian cancer (OC): A Gynecologic Oncology Group trial (GOG 158). Proc Am Soc Clin Oncol 18: 356a, 1999 (abstract 1373)
Ilson DH, Ajani J, Bhalla K, Forastiere A, Huang Y, Patel P, Martin L, Donegan J, Pazdur R, Reed C, Kelsen DP: Phase II trial of paclitaxel, fluorouracil, and cisplatin in patients with advanced carcinoma of the esophagus. J Clin Oncol 16: 1826–1834, 1998
Perez EA, Suman VJ, Krook JE, Stella PJ, Hartmann LC, Hatfield AK, Fitch T, Ingle JN: Phase II study of paclitaxel plus carboplatin as first-line chemotherapy for women with metastatic breast cancer: A North Central Cancer Treatment Group trial. Proc Am Soc Clin Oncol 17: 165a, 1998 (abstract 635)
Bajorin DF, McCaffrey JA, Hilton S, Mazumdar M, Kelly WK, Scher HI, Spicer J, Herr H, Higgins G: Treatment of patients with transitional-carcinoma of the urothelial tract with ifosfamide, paclitaxel, and cisplatin: a phase II trial. J Clin Oncol 16: 2722–2727, 1998
World Health Organization: Handbook for reporting results of cancer treatment. WHO Offset Publication No. 48. Den Haag, the Netherlands, Nijhoff, 1979
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Jones, S., Hainsworth, J., Burris, H.A. et al. Phase I Study of JM-216 (an Oral Platinum Analogue) in Combination with Paclitaxel in Patients with Advanced Malignancies. Invest New Drugs 20, 55–61 (2002). https://doi.org/10.1023/A:1014473930546
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DOI: https://doi.org/10.1023/A:1014473930546