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.