ABSTRACT
The aim of the study was to determine whether modulation of 5-fluorouracil (FU) by methotrexate (MTX) improves survival compared to FU+6-s-leucovorin (LV) following potentially curative resection of stage II and III colon cancer. Within 8 weeks from surgery, 1945 patients with stage III (44%) or high-risk stage II (55%) colon cancer were randomly assigned to receive either 6 monthly cycles of FU 370 mg m(-2) i.v. bolus preceded by LV 100 mg m(-2) i.v. bolus on days 1-5, or 6 monthly cycles of sequential MTX 200 mg m(-2) i.v. days 1 and 15 and FU 600 mg m(-2) i.v. on days 2 and 16 followed by LV rescue (15 mg given p.o. q 6 h x 6 doses). Levamisole 50 mg p.o. t.i.d. on days 1-3, every 14 days for 6 months, was planned to be given in both arms. After a median follow-up of 4.2 years, 568 patients have relapsed and 403 have died. Survival was similar with MTX --> FU and FU+LV (77 vs 77% at 5 years; P = 0.90), as were 5-year disease-free survivals (67 vs 63%; P = 0.44). Efficacy results were similar for both stage III and II patients. There were two toxic deaths, two in the MTX --> FU arm (0.2%) and zero in the control arm. We conclude that biochemical modulation of FU with LV or with MTX produces similar results in the adjuvant setting of colon cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colonic Neoplasms/drug therapy , Fluorouracil/administration & dosage , Leucovorin/administration & dosage , Methotrexate/administration & dosage , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemotherapy, Adjuvant , Colonic Neoplasms/mortality , Colonic Neoplasms/surgery , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Survival RateABSTRACT
BACKGROUND: Paclitaxel and mitoxantrone are highly active agents in the treatment of advanced breast cancer (ABC). This study evaluated the combination of paclitaxel and mitoxantrone in patients with advanced breast cancer to determine activity and toxicity. PATIENTS AND METHOD: 42 patients with ABC were treated with paclitaxel at a fixed dose of 175 mg/m2 intravenous (IV) by a 3-hour infusion on day 1, while mitoxantrone was given by 2 mg/m2 increments, starting from 10 mg/m2 by bolus IV injection on day 1 after paclitaxel. Cycles were repeated every 3 weeks. Mitoxantrone doses were increased if the maximum tolerated dose (MTD) had not been reached. RESULT: The overall response rate (CR + PR) was 69% (CI 95%: 55-83). Six (14%) patients obtained CR and 23 (55%) PR with a median duration of response of 8 months (range 2-16). There were no differences in response rates (RR) between the three levels of mitoxantrone. Median time to failure and survival were 7 months (range 1-26) and 12 months (range 2-29), respectively. After 12 months 14 (33%) patients had died and 8 (19%) patients were alive after 18 months. MTD was reached at 14 mg/m2 level of mitoxantrone. Leukopenia was evident in 39 (93%) of total patients and was severe in 28 (67%) patients. All non-hematological toxicity observed was mild. CONCLUSION: This trial shows the activity of paclitaxel and mitoxantrone in ABC and finds that a dose of 14 mg/m2 of mitoxantrone is the MTD in combination with a fixed dose of 175 mg/m2 of paclitaxel without granulocyte colony stimulating factor (G-CSF).
