The toxic and therapeutic effects obtained with a triple drug combination (BCNU, DTIC and VCR) administered in a cyclic fashion to 41 unselected evaluable patients with metastatic malignant melanoma are reported. Side effects were moderate and reversible. The overall regression rate was 44% without difference between males and females. Partial remission (> 50%) plus complete remission was 19.5% with an average duration of 5.1 months (1–20+). With the exclusion of bone lesions, all types of metastases showed regression especially those located in the soft tissues (lymph nodes and skin). The actuarial analysis of survival shows that responders live twice as long as non responders (median survival 12 months versus 6 months). However, the superior therapeutic efficacy of BCNU + DTIC + VCR over DTIC alone in metastatic melanoma remains to be demonstrated. A controlled study with different triple combinations is now in progress.
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References
1.
AhmanD. L., HannR. G.: Clinical evaluation of CCNU (NSC-79037) and a combination of imidazole carboxamide (NSC-45388) and Vincristine in the treatment of disseminated melanoma. Proc. Amer. Soc. Clin. Oncol., Abstr. n. 1, 1972.
2.
AhmanD. L., HannR. G., BiselH. F.: Clinical evaluation of 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (NSC-45388), melphalan (NSC-8806) and hydroxyurea (NSC-32065) in the treatment of disseminated malignant melanoma. Cancer Chemother. Rep., 56: 369–372, 1972.
3.
BagleyC. M.Jr., CanellosG. P., YoungR. C., GalelliJ. P., De VitaV. T.Jr.: Clinical trials with 5-(3,3-bis (2-Chloroethyl)-1-triazeno) imidazole-4-carboxamide (MSC-82196) given intravenously. Cancer Chemother. Rep., 56: 387–392, 1972.
CarterS. K.: Clinical trials and combination chemotherapy. Cancer Chemother. Rep., 2: 81–97, 1971.
6.
CarterS. K., FriedmanM. A.: 5–3,3 dimethyl-triazeno-imidazole-carboxamide (DTIC, NSC-45388), a new antitumor agent with activity against malignant melanoma. Europ. J. Cancer, 8: 85–92, 1972.
7.
CarterS. K., KrementzE. T.: Combination treatment of metastatic malignant melanoma with CCNU, VCR and DTIC. Proc. Amer. Ass. Cancer Res., 12, Abstr. n. 351, 1971.
8.
CohenS. M., GreenspanE. M., WeinerM. J., KabakowB.: Triple combination therapy of disseminated melanoma. Cancer, 29: 1489–1495, 1972.
9.
CostanziJ. J., ColtmanC. A.Jr.: Combination chemotherapy using cyclophosphamide, Vincristine, Methotrexate and 5-Fluorouracil in solid tumors. Cancer, 23: 589–596, 1969.
10.
CostanzaM. E., NathasonL., LenhardR., WolterJ., ColskyJ., OberfieldR. A., SchillingR.: Therapy of malignant melanoma with an imidazole carboxamide and bis-chloroethyl nitrosourea. Cancer, 30: 1457–1461, 1972.
11.
CowanD. H., BergsagelD. E.: Intermittent treatment of metastatic melanoma with high dose 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (NSC-45388). Cancer Chemother. Rep., 55: 175–181, 1971.
12.
GailaniS., MoonJ.: Comparative study of ICDT and combination of BCNU and VCR in the treatment of metastatic melanoma. Proc. Amer. Soc. Clin. Oncol., Abstr. n. 23, 1971.
13.
GardereS., HussainS., CowanD. H.: Treatment of metastatic malignant melanoma with a combination of 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide (NSC-45388) cyclophosphamide (NSC-26271) and Vincristine (NSC-67574). Cancer Chemother. Rep., 55: 357–361, 1972.
14.
GottliebJ. A., SerpickA. A.: Clinical evaluation of DTIC in malignant melanoma and other neoplasma: comparison of twice weekly and daily administration schedule. Oncology, 25: 225, 1971.
15.
LivingstoneR. B., CarterS. K.: Single agents in cancer chemotherapy I.F.I.Plenum Press, New York, 1970.
16.
LuceJ. K.: Chemotherapy of malignant melanoma. Cancer, 30: 1604–1615, 1972.
17.
LuceJ. K., ThurmanW. G., IsaacB. L., TalleyR. W.: Clinical trials with the antitumor agent 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (NSC-45388). Cancer Chemother. Rep., 54: 119–124, 1970.
18.
LuceJ. K., TorinB. L., PriceH.: Combination DTIC (NSC-45388), Vincristine (NSC-67574) and BCNU (NSC-409962) Chemotherapy of disseminated malignant melanoma. Proc. Amer. Ass. Cancer Res., 11: 50, Abstr. n. 198, 1970.
NathansonL., WolterJ., HortonU., ColskyJ., SchniderB. I., SchillingA.: Characteristics of prognosis and response to an imidazole carboxamide in malignant melanoma. Clin. Pharmacol. Ther., 12: 955–962, 1971.
21.
SkibbaJ. L., RamirezG., BealD. D., BryanG. T.: Preliminary clinical trial and physiological disposition of 4 (5)-(3,3-dimethyl-1-triazeno) imidazole-5 (4)-carboxamide in man. Cancer Res., 29: 1944–1951, 1969.
22.
WagnerD. E., RamirezG., WeissA. J., HillG.Jr.: Combination phase I–II study of imidazole carboxamide (NSC-45388). Proc. Amer. Soc. Clin. Oncol., Abstr. 53, 1971.
