Indomethacin-induced, monocyte-dependent restoration of local graft-versus-host reaction among cells from cancer patients.

Peripheral blood mononuclear cells from 16 of 17 cancer patients known to have a negative local graft-versus-host (GVH) reaction (T-cell function deficiency) were pharmacologically immunorestored by treatment with indomethacin. The restorative effect of the indomethacin was exerted directly on nonadherent lymphocytes. This process of desuppression required for its completion the presence of glass-adherent monocytes. The immune restorative effect of indomethacin in terms of local GVH reaction did not appear to be mediated by inhibition of prostaglandin synthesis. Pharmacologic immune restoration may be an important therapeutic modality in cancer patients.

Immune restoration and/or augmentation of local xenogeneic graft versus host reaction by Cimetidine in vitro.

The immunorestorative effect of Cimetidine in vitro on the T cell-induced local GVH reaction in vivo was studied in 43 cancer patients and 43 normal healthy donors. Both low dose (10(-5) M) and high dose (10(-4) M) Cimetidine induced significant, albeit partial, immune restoration among GVHR-negative cancer patients (p less than 0.05, p less than 0.01, respectively) with the high dose being significantly more effective (p less than 0.05). In contrast, similar Cimetidine doses induced only moderate augmentation (p greater than 0.05) among GVHR-positive cancer patients and a marginal one among normal healthy donors. In the latter 2 groups, Cimetidine was found to be occasionally detrimental in that it induced a conversion from a positive to a negative GVH reaction. These results support the concept of anti-suppressor cell activity ascribed to Cimetidine. However, the possibility of a detrimental effect should be born in mind in planning future clinical trials. We propose that the use of Cimetidine be limited to cancer patients with documented increase in suppressor cell activity associated with defective T cell function under close serial monitoring.

Phase I-II trial of percutaneous intra-arterial cis-diamminedichloro platinum (II) for regionally confined malignancy.

Forty-nine patients with regionally confined recurrent malignancy were treated with intra-arterial cis-diamminedichloro platinum II in a Phase I-II trial. A safe starting dose of 120 mg/m2 was established. An overall response rate of 45% was noted with significant responses observed among patients with melanoma, sarcoma, breast carcinoma, and neuroblastoma. Side effects included transient renal and bone marrow toxicity as well as neurotoxicity and ototoxicity (6%), the latter usually with residual damage. The rational basis and advantages of treatment with intra-arterial cis-platinum are discussed.

Intraarterial cis-platinum for patients with inoperable skeletal tumors.

Twenty-three patients with inoperable skeletal tumors were treated with intraarterial cis-platinum prior to attempted surgery. The antitumor effect of intraarterial cis-platinum was monitored clinically by radiologic imaging techniques, and whenever possible, evaluated histopathologically by examinatin of surgical or biopsy tumor specimens. Objective responses were noted in 12 patients (52%) and included 2 complete, 7 partial and 3 less-than-partial remissions lasting from 14 to 70 weeks. Limb-saving surgery or hemipelvectomy became subsequently feasible in four and one patients respectively. Preoperative intraarterial cis-platinum is a safe procedure which might be used effectively in combination with other, more conventioal postoperative adjuvant chemotherapy against skeletal tumors.