Chemoimmunotherapy of disseminated malignant melanoma with DTIC-BCG, transfer factor + melphalan

Abstract

The experimental synergism of melphalan with DTIC and the ability of transfer factor to improve immunocompetence were the basis of an attempt to improve therapeutic results in disseminated malignant melanoma. Sixty-four evaluable patients with disseminated malignant melanoma were treated in a 21-day cycle as follows: DTIC 250 mg/M2 intravenously days 1 to 5, Connaught BCG 6 X 10(8) organisms on days 7, 12, and 17 by scarification, and transfer factor 1 unit (10(9) lymphocytes equivalent, from immunocompetent relatives of patients) subcutaneously on day 12, with or without L-PAM 30 mg/M2 on day 1. Twenty-nine patients received L-PAM and 35 did not. Remission rates of 17% and 23%, respectively, occurred in these groups. An additional 15 patients received DTIC-BCG and three doses of transfer factor on days 7, 12, and 17 and had a remission rate of 20%. Remission duration and survival were compared to historical controls of 111 patients treated with DTIC and 89 treated with DTIC-BCG. Median survival on DTIC-BCG-Transfer Factor was seven months compared to four months for DTIC (P = .003) but did not differ from DTIC-BCG. Addition of L-PAM did not improve remission duration or survival compared to DTIC-BCG but enhanced myelosuppression and immunosuppression. A 60% increase in delayed type hypersensitivity to recall antigens occurred in this study compared to 34% with DTIC-BCG (P = .005). Prognosis and immunocompetence were not directly related. In summary, in this study, (1) transfer factor therapy did not enhance the clinical effects of DTIC-BCG, although it augmented delayed type hypersensitivity to recall antigens; and (2) L-PAM was not additive to DTIC in the treatment of disseminated malignant melanoma and may have abrogated the effect of immunotherapy.

Factores de transferencia en la terapéutica médica

“…En un estudio realizado en 1980 con 64 pacientes con melanoma maligno, se les dio una terapia combinada de melfalá n y dacarbazina (DTIC) má s FT para mejorar la inmunocompetencia durante 21 días, con una dosis de 250 mg/m 2 de DTIC intravenoso, bacilos de Calmette y Guerin (BCG) 6Â10 8 organismos y 1 unidad de FT (equivalente de 10 9 linfocitos), por vía subcutá nea. Los pacientes que recibieron FT tuvieron una tasa de remisió n del 20%, con un promedio de supervivencia a los cuatro meses mayor a los que no lo recibieron (p=0,003) 24 . En el modelo de rata con tumor tipo glioma multiforme se demostró que el FT de leucocitos aplicado por vía intratumoral a una dosis de 4Â10 6 y combinado con carmustina genera una reducció n del tamañ o del tumor e incrementó el nú mero de cé lulas CD2 þ , CD4 þ , CD8 þ y NK.…”