Immunotherapy (
biological therapy) comprises such things as active specific
immunotherapy ("
cancer vaccines"), nonspecific immunostimulation with
cytokines, and the inhibition of suppressor influences exerted or elicited by the
tumor. Just as
cancer chemotherapy began with the use of single agents and evolved into combination
therapy, so immunotherapeutic agents have been combined with each other and with
chemotherapy. The
alkylating agent cyclophosphamide (
Cytoxan; CY) has been used for many years to inhibit
tumor-derived suppressor influences in rodents, and has been exploited for the same use in humans. Combinations of CY and
cancer vaccines such as autologous
tumor cells,
Melacine, large multivalent immunogen (LMI), and
Theratope have been tested with some success in humans for more than a decade. In this use, the CY is a
biological response modifier rather than an
antitumor agent.
Delayed treatment with CY in treating mouse
plasmacytomas has proved more effective than immediate treatment, probably because it allows immunity to develop in the host. CY and moderate-dose
interleukin-2 (IL-2) have also been a useful regimen in treating human
melanomas.
IL-2 is itself a useful component of combination
immunotherapy, such as with
melanoma peptide vaccines, or with interferon-alfa-2b, (IFN-a), as a dual combination or part of a biochemotherapy regimen.
IL-2 and
histamine, to block
reactive oxygen species, may be a more useful combination for treatment of liver
metastases of
melanoma than
IL-2 alone. In this combination, the
histamine may permit continued, unimpeded activity of cytolytic T lymphocytes. Several different combinations of drugs and
biological agents have been used as biochemotherapy for
melanoma, but although there are higher immediate response rates, the long-range survival benefits have been marginal, not justifying the severe toxicity. Combinations of
5-fluorouracil (5-FU) and IFN-a or
levamisole have had efficacy in colon and head and
neck cancers, but here the
biological agents acted as biochemical modulators. Trials of
antibodies and
chemotherapy have been limited. It appears that
trastuzumab (
Herceptin) potentiates antitumor
therapy in
breast cancer and also increases the
cardiotoxicity of those regimens.