Beginning in 1974, patients with greater than or equal to 4 nodes positive following mastectomy were randomized to receive either 5-FU i.v. weekly or CMF i.v. every 2 weeks, both given for 12 months. Median follow-up now exceeds 112 months with nine year results below: (table; see text) Early results based on relapse-free survival favored CMF, but more patients currently are alive on the 5-FU arm. As the survival curves cross at 40 months, the 20% survival advantage for 5-FU did not achieve statistical significance. For 34% of patients failing adjuvant 5-FU, use of combination chemotherapy after relapse (commonly with CMFVP or CMF) resulted in long term survival. In contrast, long-term survival for patients failing adjuvant CMF was unusual. Relapse was detected while under weekly observation in a greater proportion of patients on 5-FU (36%) compared to CMF (6%) adjuvant treatment (p less than 0.05), potentially influencing tumor burden at recurrence. Hormonal therapy or radiation therapy as initial therapy after relapse was ineffective, with no long term survivors resulting on either arm. Weight increase on adjuvant chemotherapy was commonly seen, with weight increase greater than 10 kg associated with a poor prognosis. We conclude that initial improvement in relapse-free survival may not predict long term survival in adjuvant breast cancer trials since both the specific adjuvant therapy given pre-relapse as well as the type of salvage therapy given post-relapse may influence ultimate patient outcome.

No abstract

No abstract

The bioavailability and clinical effects of an oral controlled-release morphine sulfate tablet, MS-contin (MSC; Purdue-Frederick, Norwalk, CT) in comparison to an immediate-release (IRMS) preparation were evaluated in normal subjects and cancer patients, respectively. The inherent slow-release character of MSC was confirmed by 2 1/2 X T1/2 absorption rate, one-half Cmax, and twice Tmax relative to IRMS. The T1/2 elimination of the two morphine preparations was similar, demonstrating insignificant risk of MSC accumulation. The difference in the mean number of side effects experienced by the control group per subject was significant (.70 for MSC and 1.26 for IRMS, P = .05) and was consistent with peak plasma morphine attenuation. The cancer patients were initially switched from their previous analgesic to four hourly IRMS and then to MSC at double the dose every eight hours. The majority had their MSC dosing interval lengthened to every 12 hours with a decrease in the total daily morphine requirement. While the mean duration on MSC was 20.5 days, many patients were followed poststudy for an extended period with no appreciable development of tolerance. Overall, MSC analgesia and side effects were perceived by the patients as superior compared with prestudy opioids. The advantage of less frequent dosing may lead to improvement of the quality of life of cancer patients.