Clinical trials of irinotecan hydrochloride (CPT, campto injection, topotecin injection) in Japan.

CPT-11 was synthesized in 1984 at the laboratory of Yakult Honsha. Phase I study of CPT-11 was begun in 1986. The appropriate doses for phase II studies were decided to be 100 mg/m2 weekly or 150 mg/m2 every 2 weeks. Phase II study was conducted and this drug was approved for NSCLC, SCLC, uterine cancer and ovarian cancer by MHW in 1994. It obtained approval for stomach cancer, colorectal cancer, breast cancer, skin cancer and non-Hodgkin's lymphoma in 1995. The combination chemotherapies including CPT-11 have been conducted by using various regimens such as CPT-11 + CDDP, CPT-11 + VP-16, CPT-11 + 5-FU and CBDCA + CPT-11. In stage IV SCLC two prospective randomized controlled trials are on going comparing CPT-11 vs. CPT-11 + CDDP vs. VDS + CDDP and CPT-11 + CDDP vs. VDS + CDDP. In advanced SCLC Japanese Clinical Oncology Group (JCOG) started a randomized controlled trial comparing CPT-11 + CDDP vs. VP-16 + CDDP. In stage III NSCLC the dose escalation studies of CPT-11 (CPT-11) in the combination with TRT are ongoing by JCOG. The problem of CPT-11 in the combination chemotherapy and combined modality is that it is quite difficult to increase the dose of CPT-11 to full dose to obtain the maximum effect.