Tamoxifen-augmented biochemotherapy (Interferon-α-2b, Tamoxifen, BCNU, CDDP, DTIC) for malignant melanoma

Abstract

Depending on the metastatic pattern involved, therapeutic approaches in metastatic malignant melanoma are primarily focused on the surgical reduction of tumor masses (if solitary or operable) and palliation of disseminated disease. Despite major efforts to improve the efficacy of cytotoxic drug regimens, longterm survival or even cure is usually almost unfeasible once dissemination of disease has commenced. However, the administration of bi-omodulatory and/or immunomodulatory compounds has prompted broad investigational efforts since it had been demonstrated that neoplastic tumor growth can be modulated. Among others, the anti-hormonal agent Tamoxifen (TAM) has manifold biological properties that are approached to be exploited in cancer therapy [1]. Previous reports on combination therapy together with cytotoxic agents revealed promising palliative results exceeding those obtained by cytotoxic treatment only [8–12]. The investigational ITBCD protocol described here deals with sequential combination of TAM together with Interferon-α-2b preceding cytotoxic combination chemotherapy consisting of BCNU, DTIC, and Cisplatin. The modalities used are arranged sequentially (phase 1–3) and superimposed synergistically thus exerting overlapping biological effects (phase 1: « Induction »; phase 2: « Priming »; phase 3: « Cytotoxic »). They are outlined to pharmacodynamically prime melanoma metastasis and thus augment the efficacy of cytotoxic compounds used.