A comparison of intermittent vs. continuous and of adriamycin vs. methotrexate 5-drug chemotherapy for advanced breast cancer. A Cancer and Leukemia Group B study.

The therapeutic effectiveness of intermittent vs. continuous combination chemotherapy and of the substitution of adriamycin for methotrexate in a 5-drug regimen was evaluated in women with metastatic breast carcinoma. Patients were randomly allocated to receive continuous therapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone ( CMFVP -C, 86 patients), intermittent CMFVP ( CMFVP -I, 109 patients), or intermittent CAFVP (107 patients). The CR + PR rate with CAFVP (71%) was superior to CMFVP -C (50%, p = 0.003) and to CMFVP -I (50%, p = 0.002). The remission duration with CAFVP (14 months, median) was superior to CMFVP -I (7 months) (p less than 0.01), and tended to be superior to CMFVP -C (9 months) (p = 0.07). There was a survival advantage of CAFVP (19 months, median) over CMFVP -I (13 months) (p = 0.01), but not over CMFVP -C (16 months) (p = 0.24). Among CR + PR patients, the survival with CAFVP (29 months, median) was superior (p = 0.02) to both CMFVP -I (18 months) and CMFVP -C (21 months). The CMFVP -C regimen was associated with the highest incidence of leukopenia and neurologic toxicity, but the lowest incidence of GI toxicity. The results indicate that the CAFVP regimen is well tolerated and is superior to the CMFVP regimens.

Evidence for the independence of brainstem mechanisms mediating analgesia induced by morphine and two forms of stress.

Exposure to inescapable footshock stress causes potent analgesia in the rat. According to several criteria, prolonged, intermittent footshock elicits analgesia mediated by opioid peptides, whereas brief, continuous footshock produces non-opioid analgesia. We now report that these neurochemically discrete forms of stress analgesia also have different neuroanatomical bases. Electrolytic lesions damaging greater than 85% of the n. raphe magnus ('complete' NRM lesions), but not lesions of the same size causing less NRM damage (partial NRM lesions) significantly reduce only the non-opioid form of stress analgesia. In the same animals, complete and partial NRM lesions disrupt morphine analgesia; however, our analyses indicate that this effect is not mediated by the same substrate involved in either form of stress analgesia. These results support the existence of multiple endogenous analgesia mechanisms and indicate a complex role for the NRM in these systems.

A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer.

Women with breast carcinoma and four or more involved ipsilateral axillary lymph nodes were randomly assigned to receive an induction course and 2 yr of maintenance chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF, 150 patients), CMF plus vincristine and prednisone (CMFVP, 166 patients), or chemoimmunotherapy with CMF plus the methanol extraction residue of BCG (CMF-MER, 85 patients). After 5 yr of accrual and a median follow-up of 34 mo, CMFVP is superior to CMF (p less than 0.01) with disease-free survival estimates at 4 yr of 60% for CMFVP compared to 45% for CMF. The disease-free survival advantage of CMFVP over CMF was greater in postmenopausal (p = 0.02) than in premenopausal patients (p = 0.09). CMF-MER was similar to CMF alone. CMF related side effects were similar in each regimen (see text), except for a greater incidence of leukopenia during induction with CMF than with CMFVP (p less than 0.01).

A randomized trial of postoperative five-versus three-drug chemotherapy after mastectomy: a Cancer and Leukemia Group B (CALGB) study.

The Cancer and Leukemia Group B (CALB) has conducted a randomized study of adjuvant chemotherapy in patients with breast cancer who have involved axillary nodes at the time of mastectomy. Five-drug treatment (CMFVP) was compared with three-drug treatment (CMF). For patients with more than three involved nodes, the CMFVP regimen produced a significantly prolonged disease-free survival in comparison to the CMF regimen.

Venous thrombosis during multimodal treatment of primary breast carcinoma.

In a cooperative group study of 433 breast cancer patients treated with 2 years of postmastectomy chemotherapy, 22 (5%) developed venous thromboses of various types. Two patients died. None of the patients had demonstrable tumor metastases at the time of the venous thrombosis, although seven had metastases a median of 11 months after the thromboses. Thirteen living patients have not had tumor recurrences. No patient developed thrombosis after the chemotherapy was completed. It is possible that one or more of the chemotherapeutic agents initiated the clotting problems. Thrombophlebitis is a possible problem occurring during adjuvant chemotherapy for breast cancer and requires prompt treatment.