[Non-cross-resistant sequential combination chemotherapy consisting of cis-diammine-dichloroplatinum (II) mainly, based on synchronization theory, in human bladder cancer xenografts in athymic nude mice].

We examined the chemotherapies with cis-diamminedichloroplatinum (II) (CDDP) alone and in combination, using the human bladder cancer xenografts (BT-8 and BT-11 strains) in athymic nude mice (BALB/C), to establish the most effective and useful method for urothelial cancer in clinical use. First, to assess the anti-tumor activities of single-drug and our devised VPM or CisCF combination chemotherapies, experiments were done using the BT-8 strain bladder cancer (transitional cell carcinoma and grade III). The schedule and dosage of each chemotherapy were as follows. Vincristine (VCR): 0.06 mg/kg, days 1-6, peplomycin (PEP): 0.9 mg/kg, days 1-6, methotrexate (MTX): 0.6 mg/kg, days 1-6, cytosine arabinoside (Ara-C): 3 mg/kg, days 1-6, 5-fluorouracil (5-FU): 30 mg/kg, days 1-6, adriamycin (ADM): 3 mg/kg, days 1-6, cyclophosphamide (CPM): 10 mg/kg, days 1-10, and CDDP: 2.5 mg/kg, days 1-6. These were for single-drug chemotherapies. The VPM combination consisted of VCR (0.06 mg/kg, days 1 and 4), PEP (0.3 mg/kg, days 1-6) and MTX (0.3 mg/kg, days 2, 3, 5 and 6), and the CisCF combination consisted of CDDP (2.5 mg/kg, days 1 and 4), Ara-C (3 mg/kg, days 1 and 4) and 5-FU (15 mg/kg, days 2, 3, 5 and 6). The control group was given normal saline of 0.1 ml/20 g body weight, intraperitoneally. All anti-cancer drugs were also given intraperitoneally. Secondly, to assess the anti-tumor activities of CDDP alone and various modes of combination chemotherapies with or without CDDP, the following experiments were done using the BT-11 strain bladder cancer (a mixed type of transitional cell carcinoma and squamous cell carcinoma). CDDP: 2.5 mg/kg, days 1-6. VPM X 2: VCR (0.04 mg/kg, days 1, 4, 8 and 11), PEP (0.2 mg/kg, days 1-4) and MTX (0.2 mg/kg, days 2, 3, 5, 6, 9, 10, 12 and 13). CisCF X 2: CDDP (2.5 mg/kg, days 1 and 8), Ara-C (3 mg/kg, days 1, 6, 8 and 13) and 5-FU (30 mg/kg, days 3, 4, 5, 10, 11 and 12). VPM-CisCF (I): VCR (0.04 mg/kg, days 1 and 4), PEP (0.2 mg/kg, days 1-7), MTX (0.2 mg/kg, days 2, 3, 5 and 6), CDDP (2.5 mg/kg, day 8), Ara-C (3 mg/kg, days 8 and 13), and 5-FU (30 mg/kg, days 10-12).(ABSTRACT TRUNCATED AT 400 WORDS)