Summary
Oxaliplatin, or trans-1-diaminocyclohexane-platinum, was tested in a phase I study. A total of 44 patients received 116 courses with dose escalation from 45 to 200 mg/m2. Neither renal nor hematologic toxicities were observed at doses up to 200 mg/m2. Gastrointestinal toxicity was practically constant and often of grade 3–4 on the WHO scale (53% of patients). The dose-limiting toxicity was a peculiar sensory neuropathy; the first neurologic phenomena appeared at a dose of 135 mg/m2 and continued thereafter, occurring after 75% of the courses with mild to moderate intensity (WHO grade 1–2 after 67% of the courses). Neurotoxicity was cumulative and six patients developed grade 3 disabling neuropathy after a cumulative dose of 500 mg/m2, with walking and handwriting difficulties being slowly regressive in three cases. A peculiar symptom was the influence of temperature, with exacerbation of paresthesias when patients touched cold surfaces. Nerve-conduction studies carried out in six cases showed a predominantly sensory neuropathy with axonal degeneration. No other toxicities were observed, although audiograms were not systematically done. We observed four partial responses that lasted 6–13 months in patients with oesophageal (2 cases), lung (1), and urothelial cancer (1); two of these patients had been pretreated with cisplatin. Since neurologic side effects occur very frequently and may produce a long-lasting sensory neuropathy, for phase II studies we recommend a starting dose of 135 mg/m2, with a careful neurologic survey.
Similar content being viewed by others
References
Al Kourainy K, Kish J, Ensley J (1987) Achievement of superior survival for histologically negative versus histologically positive clinically complete responders to cisplatin combination chemotherapy in patients with locally advanced head and neck cancer. Cancer 59:233–238
Beecher R, Schutt P, Osieka R, Schmidt CG (1980) Peripheral neuropathy and ophthalmologic toxicity after treatment withcis-dichlorodiamminoplatinum (II). J Cancer Res Clin Oncol 96:219–221
Bradner WT, Rose WC, Huftalen JB (1980) Antitumor activity of platinum analogs. In: Cisplatin: current status and new developments. (Prestayko, New York, pp 171–182
Forastiere AA, Takasugi BJ, Baker SR, Wolf GT, Kudla-Hatch V (1987) High-dose cisplatin in advanced head and neck cancer. Cancer Chemother. Pharmacol 19:155–158
Gandara D, Gregorio M de, Wold H, Wilbur BJ, Kohler M, Lawrence HJ, Deissroth AB, George CB (1986) Modified dose schedule of high-dose cisplatin. Reduced toxicity and correlation with plasma pharmacokinetics. A Northern California Oncology Group pilot study in non-small-cell lung cancer. J Clin Oncol 4:1787–1793
Gastaut JL, Pellissier JF, Jean P, Tubiana N, Carcassonne Y (1982) Neuropathie périphérique au cisplatine. Une observation. Nouv Presse Med 11:1113–1117
Hadley D, Herr HW (1979) Peripheral neuropathy associated withcis-dichlorodiammine platinum(II) treatment. Cancer 44:2026–2028
Kedar A, Cohen ME, Freeman AI (1978) Peripheral neuropathy as a complication ofcis-dichlorodiammine platinum(II) treatment: a case report Cancer Treat Rep 62: 819–821
Kidani Y, Inagaki K (1978) Antitumor activity of 1,2-diaminocyclohexane-platinum complexes against sarcoma-180 ascites form. J Med Chem 21:1315–1318
Kidani Y, Inagaki K, Isukagoshi S (1976) Examination of antitumor activities of platinum complexes of 1,2-diaminocyclohexane isomers and their related complexes. Jpn J Cancer Res 67:921–922
Kidani Y, Noji M, Tashiro T (1980) Antitumor activity of platinum(II) complexes of 1,2-diamino cyclohexane isomers. Jpn J Cancer Res 71:637–643
Legha SS, Dimery IW (1985) High dose cisplatin administration without hypertonic saline: observation of disabling neurotoxicity. J Clin Oncol 3:1373–1378
Manas A, Cubillo S, Alonso E (1979) Monitoring peripheral neurotoxicity from cis-platinum (DDP). Abstracts of the 5th Annual Meeting of the Medical Oncology Society, Nice, December 5–7, p 31
Mathe G, Kidani Y, Noji M, Maral R, Bourut C, Chenu E (1985) Antitumor activity of 1-OHP in mice. Cancer Lett 27: 135–143
Mathe G, Kidany Y, Triana K, Brienza S, Ribaud P, Goldschmidt E, Esctein E, Despax R, Musset M, Misset JL (1986) A phase I trial of trans-1-diaminocyclohexane oxalatoplatinum (1-OHP). Biomed Pharmacother 40:372–376
Merrin CE (1979) Treatment of genitourinary tumors withcis-dichlorodiammine platinum(II): experience in 250 patients. Cancer Treat Rep 63:1579–1584
Ostrow S, Egorin MJ, Hahn D, Markus S, Leroy A, Chang P, Klein M, Bachur NR, Wiernik PH (1980)cis-Dichlorodiammine platinum and Adriamycin therapy for advanced gynecological and genitourinary neoplasms. Cancer 46: 1715–1721
Ozols RF, Corden BJ, Jacob J, Wesley MN, Ostchega Y, Young RC (1984) High dose cisplatin in hypertonic saline. Ann Intern Med 100:19–24
Ozols RF, Ostchega Y, Meyers CE, Young RC (1985) High dose cisplatin in hypertonic saline in refractory ovarian cancer. J Clin Oncol 3:1246–1250
Panettiere FJ (1981) Cisplatinum toxicity: an analysis based on three SWOG studies. Proc Am Assoc Cancer Res 22:157
Roelofs RI, Hrushesky W, Rogin F, Rosenberg GL (1984) Péripheral sensory neuropathy and cisplatin chemotherapy. Neurology 34:934
Trugman J, Hogenkamp HPC, Roelofs R (1985) Cisplatin neurotoxicity: failure to demonstrate vitamin B12 inactivation. Cancer Treat Rep 69:453–455
Trump DL, Hortvet L (1985) Etoposide and very high dose cisplatin: salvage therapy for patients with advanced germ cell neoplasms. Cancer Treat Rep 69:259–261
Von Hoff DD, Reichert CM, Cuneo R, Reddick R, Gallagher M, Rozencweig M (1979) Demyelination of peripheral nerves associated withcis-diamminedichloroplatinum(II) (DDP) therapy. Proc Am Assoc Cancer Res ASCO 20:91
Wiltshaw E (1985) Ovarian trials at the Royal Marsden. Cancer Treat Rev 12:67–71
Young RC, Fuks Z, Knapp R (1985) Cancer of the ovary. In: De Vita V Jr, Hellman S, Rosenberg SA (eds) Cancer: principles and practice in oncology. Lippincott, Philadelphia, pp 1083–1117
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Extra, J.M., Espie, M., Calvo, F. et al. Phase I study of oxaliplatin in patients with advanced cancer. Cancer Chemother. Pharmacol. 25, 299–303 (1990). https://doi.org/10.1007/BF00684890
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00684890