Abstract
The use of mitomycin for metastatic colorectal cancer has been limited by mitomycin's myelosuppressive potential. The objective of this randomized study was to determine whether WR-2721 would decrease the hematologic toxicity of mitomycin in patients with colorectal cancer resistant to fluorouracil-based therapy. Ninety-seven patients with refractory colorectal cancer were randomized to receive either mitomycin 20 mg/m2 only or the same dose, of mitomycin after pretreatment with WR-2721, 910 mg/m2. The principal toxicity in both groups was thrombocytopenia. The platelet nadirs were lower in patients receiving single-agent mitomycin (P=0.026). Surprisingly, no clinical complete or partial responses were noted in either group, and survival was not different between the two groups. Thus, while WR-2721 decreased the thrombocytopenia associated with mitomycin therapy, mitomycin was ineffective in the treatment of refractory colorectal carcinoma.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ansfield F (1969) Clinical study of mitomycin-C (NSC 26980) in colorectal cancer. Cancer Chemother Rep [I] 53: 287
Baker LH, Izbicki RM, Vaitkevicius VK (1976) Phase II study of porfiromycin vs. mitomycin-C utilizing acute intermittent schedules. Med Pediatr Oncol 2: 207
Glick J, Kemp G, Rose P, McCulloch W, Scheffler B, Schein P (1992) A randomized trial of cyclophosphamide and cisplatin ± WR-2721 in the treatment of advanced epithelial ovarian cancer. Proc Am Soc Clin Oncol 11: 258
Glover D, Glick JH, Weiler C, Hurowitz S, Kligerman MM (1986) WR-2721 protects against the hematologic toxicity of cyclophosphamide: a controlled phase II trial. J Clin Oncol 4: 584
Glover D, Grabelsky S, Fox K, Weiler C, Cannon L, Glick J (1989) Clinical trials of WR-2721 and cisplatinum. Int J Radiat Oncol Biol Phys 16: 1201
Godfrey T, Wilbur D (1972) Clinical experience with mitomycin in large infrequent doses. Cancer 29: 647
Kemeny N, Israel K, Niedzwiecki D, Chapman D, Botet J, Minsky B, et al (1990) Randomized study of continuous infusion fluorouracil vs. fluorouracil plus cisplatin in patients with metastatic colorectal cancer. J Clin Oncol 8: 313
Kish J, Ensley J, Al-Saraff M (1992) Evaluation of WR-2721 + cisplatin + 5-fluorouracil (5FU) infusion in patients with recurrent advanced head and neck cancer. Proceedings of the third International Conference on Head and Neck Cancer 116: 79
Lokich J, Ahlgren JD, Gullo J, Philips JA, Fryer JG (1989) A prospective randomized comparison of continuous infusion fluorouracil with conventional bolus schedule in metastatic colorectal carcinoma: a mid-Atlantic Oncology Program Study. J Clin Oncol Cancer Res 7: 425
Moertel C, Reitmeier R, Hahn R (1968) Mitomycin-C therapy in advanced gastrointestinal cancer. JAMA 20: 1045
Moore GE, Bross IDJ, Ausman S, Nadler S, Jones R Jr, Slack N, et al (1968) Effects of mitomycin-C in 346 patients with clinically advanced cancers. Cancer Chemother Rep [I] 52: 67
Seifert P, Baker LH, Reed ML, Vaitkevicius V (1975) Comparison of continuously infused 5-fluorouracil with bolus injection in the treatment of patients with colorectal adenocarcinoma. Cancer 6: 123
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Poplin, E.A., LoRusso, P., Lokich, J.J. et al. Randomized clinical trial of mitomycin-C with or without pretreatment with WR-2721 in patients with advanced colorectal cancer. Cancer Chemother. Pharmacol. 33, 415–419 (1994). https://doi.org/10.1007/BF00686271
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00686271