COP-BLAM multidrug infusion chemotherapies for lymphoma: results in a community hospital setting.

Twenty-two patients with malignant lymphoma were treated with three different COP-BLAM infusional chemotherapy protocols at the Jersey Shore Medical Center. The treatment group included 18 patients with large-cell lymphoma, 3 patients with Hodgkin's disease, and 1 patient with composite lymphoma (large-cell lymphoma and Hodgkin's disease). Three patients were treated with COP-BLAM III, 9 with COP-BLAM IV, and 10 with COP-BLAM V. The age of the patients at diagnosis ranged from 18 to 74 years, with a median age of 64 years. One patient had stage I bulky disease, 4 had stage II bulky disease, 3 had stage III disease, and 14 had stage IV disease. Twenty patients were evaluable for response; 2 were too early to evaluate. Complete response (CR) was seen in 18 of the 20 evaluable patients (90%). Potential cure (excludes non-lymphoma-related deaths) at 24 months is projected at 78%. Eleven patients are presently without disease and off therapy (55%). Projected failure-free survival at 2 years is 71% (a failure being death from any cause). Eleven of 22 patients developed 15 febrile episodes. Vincristine neuropathy was seen in 6 patients. Subclinical pulmonary fibrosis was seen in 1 patient. There was one cardiotoxic death. The COP-BLAM infusional protocols are highly effective, tolerable regiments that are applicable in community hospitals and can yield good response rates, with a high percentage of disease-free survivors in all age groups. The treatment can be completed in a short period with acceptable toxicity.

Evaluation of a sequential 5-FU and hydroxyurea combination in advanced bowel cancer.

Twenty-nine patients (two with small bowel cancer and 27 with colorectal cancer) were treated with a sequential 5-FU-hydroxyurea combination following the suggestion of schedule-dependent synergism in experimental systems. No enhanced toxicity was observed, but the response rate was only 4%. Seven additional patients manifested greater than or equal to 50% declines in CEA, but caution must be used in interpreting such changes as antitumor activity.

A new mechanism for tumor induced platelet aggregation. Comparison with mechanisms shared by other tumor with possible pharmacologic strategy toward prevention of metastases.

Because tumor-induced platelet aggregation appears to play a role in the development of certain experimental tumor metastases, we examined the mechanism(s) of tumor-induced platelet aggregation as well as the effect of various anti-platelets agents. Two mechanisms for tumor-induced platelets aggregation have been previously described: (1) a mechanism which requires complement, a stable plasma factor, divalent cation and a sialo-lipo-protein vesicular component of the tumor membrane for platelet aggregation; and (2) a mechanism which operates via the generation of thrombin and requires a phospholipid component of the tumor membrane. We now report a new mechanism of tumor-induced platelet aggregation which is shared by three different tumors: a spontaneously metastatic human melanoma, HM29, a murine melanoma, B16F10, and a carcinogen-induced metastatic murine colon carcinoma, CT26. These tumors do not require cell-surface sialic acid or serum complement as does the first mechanism. They do not require cell-surface phospholipid, as do the tumors representing the other two mechanism. They do not aggregate platelets via the generation of thrombin as do tumors representing the second mechanism. These tumors are unique in that they require a trypsin-sensitive surface protein for activity. The ability of the thrombin-generating tumors to aggregate platelets is uniquely sensitive to two highly specific, synthetic thrombin-competitive inhibitors: DAPA and No. 805. The other two groups of tumors are at least 10 times more sensitive to inhibition of platelet aggregation by elevation of cyclic AMP levels (prostacyclin, 6-keto-PGE1, dibutyryl cyclic AMP) and at least 10 times more sensitive to inhibition of prostaglandin synthesis (indomethacin, ibuprofen). Thus, tumor-induced platelet aggregation is heterogeneous with respect to mechanism of action as well as inhibition by anti-platelet pharmacologic agents. Sensitivity to anti-platelet agents correlates with the mechanism by which tumor cells aggregate platelets.