This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sasaki, Y. Articles by Saijo, N. Search for Related Content PubMed PubMed Citation Articles by Sasaki, Y. Articles by Saijo, N.

Phase I Study and Pharmacological Analysis of cis-Diammine(glycolato)platinum (254-S; NSC 375101D) Administered by 5-Day Continuous Intravenous Infusion¹

Department of Medical Oncology, National Cancer Center Hospital, 1-1 Tsukiji 5-Chome, Chuo-ku, Tokyo 104 [Y. S., M. M., T. S., K. E., T. T., Y. O., A. K.]; Shionogi Research Laboratories, 12-4 Sagisu 5-Chome, Fukushima-ku, Osaka 553 [T. A.]; and Pharmacology Division, National Cancer Center Research Institute [N. S.], Japan

A phase I study of cis-diammine(glycolato)platinum (254-S; NSC 375101D) was conducted in 15 patients with refractory or relapsing malignancy by 5-day continuous i.v. infusion. Three to 5 patients per dose were given 50, 75, 87.5, or 100 mg/m²/120 h (10–20 mg/m² daily for 5 days). Toxicity evaluation and pharmacokinetic analysis were performed in 15 and 14 patients, respectively. Thrombocytopenia and neutropenia were the dose-limiting toxicities at the maximum tolerated dose of 87.5 mg/m²/120 h (17.5 mg/m²/day); however, nonhematological toxicities including renal toxicity, nausea and vomiting, and peripheral neuropathy were mild and well tolerated. The nadir of platelets and neutrophils was observed 4 and 5 weeks, respectively, after the initiation of drug infusion. Plasma and urine samples were obtained during and after infusion for quantification by atomic absorption spectrophotometry of total and free platinum levels derived from 254-S. The maximum level of total platinum was obtained after 120 h of infusion, whereas the steady state concentration of free platinum in the patients given 75 mg/m² or more was over 0.1 µg/ml. Free platinum levels declined monophasically, with half-lives of 0.65–2.56 h/100 mg/m² dose. The mean area under the concentration versus time curve (AUC) in the patients treated with 75 mg/m² was 1069 µg/ml min, which was similar to that obtained in the patients receiving 100 mg/m² of 254-S by i.v. drip infusion over 30 min. There was a direct correlation between the dose administered and the AUC of platinum (R = 0.757, P = 0.002) or the steady state plasma concentration of free platinum (R = 0.763, P = 0.002). The percentage of platinum excreted in urine 144 h after the initiation of infusion ranged from 73.1 to 100% for each dose level. No significant relationship was established between creatinine clearance in patients before treatment and the AUC or steady state concentration of free platinum. The plasma platinum AUC showed a linear correlation with the percentage of change in leukocytes (R = 0.736, P = 0.003). In conclusion, the recommended phase II dose for a continuous infusion of 254-S is 75.5 mg/m²/120 h every 6 weeks.

¹ Supported in part by Grants-in-Aid for cancer research from the Ministry of Health and Welfare of Japan and from Shionogi Pharmaceutical Company.

² To whom requests for reprints should be addressed, at National Cancer Center Hospital, Department of Medical Oncology, 1-1 Tsukiji 5-Chome, Chuoku, Tokyo 104, Japan.

Received 6/21/90. Accepted 12/20/90.

This article has been cited by other articles:

				Y. Shioyama, K. Nakamura, S. Ohga, S. Nomoto, T. Sasaki, T. Yamaguchi, T. Toba, T. Yoshitake, H. Terashima, and H. Honda Radiation Therapy for Recurrent Esophageal Cancer after Surgery: Clinical Results and Prognostic Factors Jpn. J. Clin. Oncol., December 1, 2007; 37(12): 918 - 923. [Abstract] [Full Text] [PDF]

				N. Fuwa, T. Kodaira, H. Tachibana, T. Nakamura, and T. Daimon Dose Escalation Study of Nedaplatin with 5-Fluorouracil in Combination with Alternating Radiotherapy in Patients with Head and Neck Cancer Jpn. J. Clin. Oncol., March 1, 2007; 37(3): 161 - 167. [Abstract] [Full Text] [PDF]

				Y. Nishimura, R. Koike, K. Nakamatsu, S. Kanamori, M. Suzuki, H. Shigeoka, and H. Shiozaki Concurrent Chemoradiotherapy with Protracted Infusion of 5-FU and Cisplatin for Postoperative Recurrent or Residual Esophageal Cancer Jpn. J. Clin. Oncol., July 1, 2003; 33(7): 341 - 345. [Abstract] [Full Text] [PDF]

				A. Kitami, T. Suzuki, Y. Kamio, and S. Suzuki Chemotherapy of Thymic Carcinoma: Analysis of Seven Cases and Review of the Literature Jpn. J. Clin. Oncol., December 1, 2001; 31(12): 601 - 604. [Abstract] [Full Text] [PDF]

				H. Sumi, A. Ohtsu, N. Boku, M. Muto, F. Nagashima, K. Hosokawa, S. Yoshida, M. Satake, S. Ishikura, and T. Ogino A Case of Inoperable Esophageal Carcinoma with Hepatic and Nodal Metastases Which Showed a Long-term Survival after Chemoradiotherapy Including Nedaplatin Jpn. J. Clin. Oncol., September 1, 2000; 30(9): 406 - 409. [Abstract] [Full Text] [PDF]