TY - JOUR
T1 - Difluoromethylornithine and leukocyte interferon
T2 - A phase I study in cancer patients
AU - Talpaz, M.
AU - Plager, C.
AU - Quesada, J.
AU - Benjamin, R.
AU - Kantarjian, H.
AU - Gutterman, J.
N1 - Funding Information:
Accepted 20 November 1985. *The research was supported by grants from the Interferon Foundation and Merrell Dow Pharmaceutical Corporation. Research conducted in part by the Clayton Foundation for Research, and the James E. Lyon Foundation. Dr. Gutterman is a senior Clayton Foundation investigator. fTo whom all correspondence should bc addressed.
PY - 1986/6
Y1 - 1986/6
N2 - Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and human leukocyte interferon (IFN-α) have synergistic anti-tumor activities in vivo in B 16 melanoma and in vitro against several human cancer cell lines. We have, therefore, carried out a phase I combination study with DFMO plus alpha interferon in the following manner: DFMO was maintained at a steady dose for the first four levels, 1.5 g/m2 every 6 hr. IFN-α was given in 100% increments ranging from 0.4 × 106U/m2 to 3.2 × 106U/m2 i.m. daily. At the fifth dose level both IFN-α and DFMO were raised by 100 and 50% respectively. From levels one through four the combination was well tolerated with no dose interruptions required because of G.I. toxicity or myelosuppression. However, at dose level 5, one-third of the patients required dose cessation and decrease due to nausea, vomiting and diarrhea. We conclude that for phase II studies the maximal tolerated dose is 3.2 million units of IFN-α/m2 and 1.5 g/m2 of DFMO every 6 hr. Of 12 patients with metastatic melanoma, 2 had partial remissions lasting 58+ and 36+, weeks. Two additional patients had minor responses lasting 29 and 32+, weeks. Minor responses were observed in a patient with colon carcinoma and a patient with renal carcinoma. The clinical activity of the combination is currently being pursued in a phase II study among patients with metastatic malignant melanoma.
AB - Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, and human leukocyte interferon (IFN-α) have synergistic anti-tumor activities in vivo in B 16 melanoma and in vitro against several human cancer cell lines. We have, therefore, carried out a phase I combination study with DFMO plus alpha interferon in the following manner: DFMO was maintained at a steady dose for the first four levels, 1.5 g/m2 every 6 hr. IFN-α was given in 100% increments ranging from 0.4 × 106U/m2 to 3.2 × 106U/m2 i.m. daily. At the fifth dose level both IFN-α and DFMO were raised by 100 and 50% respectively. From levels one through four the combination was well tolerated with no dose interruptions required because of G.I. toxicity or myelosuppression. However, at dose level 5, one-third of the patients required dose cessation and decrease due to nausea, vomiting and diarrhea. We conclude that for phase II studies the maximal tolerated dose is 3.2 million units of IFN-α/m2 and 1.5 g/m2 of DFMO every 6 hr. Of 12 patients with metastatic melanoma, 2 had partial remissions lasting 58+ and 36+, weeks. Two additional patients had minor responses lasting 29 and 32+, weeks. Minor responses were observed in a patient with colon carcinoma and a patient with renal carcinoma. The clinical activity of the combination is currently being pursued in a phase II study among patients with metastatic malignant melanoma.
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U2 - 10.1016/0277-5379(86)90166-5
DO - 10.1016/0277-5379(86)90166-5
M3 - Article
C2 - 3091371
AN - SCOPUS:0022495327
SN - 0277-5379
VL - 22
SP - 685
EP - 689
JO - European Journal of Cancer and Clinical Oncology
JF - European Journal of Cancer and Clinical Oncology
IS - 6
ER -