[An early phase II clinical study of YM 294 (rhlL-11) in patients with solid tumors and malignant lymphoma].

An early phase II study was conducted to examine the efficacy and safety of YM 294 on chemotherapy-induced thrombocytopenia in patients with solid tumors and malignant lymphoma. The response rates which were judged as having good or excellent efficacy by the investigators were 66.7% in all groups with 25 microg/kg or more, and the increase in nadir platelet counts and decrease in platelet transfusions were observed. Adverse reactions were fever, edema, abnormal electrocardiogram and weight gain. All adverse reactions as well as abnormal changes in laboratory values for which the casual relationship with the study drug could not be excluded were resolved and proved to be not serious. The results of this study suggest the efficacy of YM 294 at 25 microg/kg or more for chemotherapy-induced thrombocytopenia in patients with solid tumors and malignant lymphoma. It was considered that a study should be performed to assess the efficacy and safety of YM 294 using a dose of 25 microg/kg or more in the future.

Japanese ovarian trials: focus on irinotecan.

Irinotecan (CPT-11, Camptosar) has achieved a response rate of 23.6% in recurrent ovarian cancer. Irinotecan/cisplatin combination chemotherapy has shown a response rate of 33% in platinum-resistant ovarian cancer, and 76% when used as the initial regimen for ovarian cancer. Regarding dose-limiting toxicity, although neutropenia and diarrhea were observed, diarrhea was thought to cause no remarkable problems in the combination regimen examined. Based on these results, irinotecan is considered to be a useful drug in chemotherapy for ovarian cancer.

Clinical usefulness of macrophage colony-stimulating factor for ovarian cancers: Long-term prognosis after five years.

We performed a randomized double blind study between 1992 and 1995 in which 214 patients with FIGO stage I to III ovarian cancers received administration of 10(6) units (low dose group) or 8x10(6) units (high dose group) of macrophage colony-stimulating factor (M-CSF) after cyclophosphamide/adriamycin/cisplatin (CAP) therapy. The period required to finish a set of intensive chemotherapy, which was the primary endpoint, was significantly shortened (p=0.0004), and the incidence of febrile neutropenia significantly decreased (p=0.04). In this study, we followed the patients for a prolonged period. The patients were divided into two groups: patients with complete tumor excision and those with incomplete excision, then the relapse rate and survival rate 5 years after initiation of the clinical study were compared. The relapse rate tended to be lower in the high dose group than in the low dose group in patients with no residual tumor (p=0.0750). However, there was no difference in the relapse rate between the two dose groups in patients with residual tumor. Although there were no significant differences in the survival rate between the high and low dose groups in patients with or without residual tumor, the survival rate in mucinous adenocarcinoma patients with no residual tumor was 64.3% in the low dose group (n=14) and 92.3% in the high dose group (n=14), showing a significantly higher rate (p=0.0436), and the survival rate tended to be higher in the high dose group in patients with serous adenocarcinoma (p=0.0786). Furthermore, in patients aged 40 years or younger with no residual tumor, the survival rates were 73.9 and 100% in the low and high dose groups, respectively, showing a significantly higher rate in the high dose group (p=0.0310). Our results suggest that administration of M-CSF can improve the long-term prognosis of ovarian cancer patients with no residual tumor, but further prospective randomized trials with a primary endpoint of relapse-preventing effect are needed.

Irinotecan (CPT-11) and cisplatin as first-line chemotherapy for advanced ovarian cancer.

OBJECTIVE: To evaluate the efficacy and toxicity of a combination of irinotecan (CPT-11) and cisplatin as first-line chemotherapy in advanced ovarian cancer. METHODS: Twenty-six patients with previously untreated advanced epithelial ovarian cancer were enrolled in this study. CPT-11 60 mg/m(2) was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m(2) on day 1. Cycles were repeated every 28 days for at least two cycles. The median patient age was 55 years (range, 37-75), and the median performance status was 1. RESULTS: Objective responses were recorded in 19 of 25 eligible patients (76%; 95% confidence interval, 55-91%). Complete responses were obtained in 2 patients (8%), and partial response in 17 patients (68%). Stable disease was recorded in 2 patients (8%) and progressive disease in 2 (8%). The median time to response was 62 days (range, 28-234 days). The median survival time for all 25 patients was 30.9+ months (range, 4.1-60.0+ months). The major toxic effects were leukopenia, neutropenia, and diarrhea. Grade 3 or 4 leukopenia, neutropenia, and diarrhea occurred in 17 (68%), 20 (83.3%), and 5 patients (20%), respectively. Thrombocytopenia was less common. No treatment-related deaths occurred. CONCLUSION: The combination of CPT-11 and cisplatin showed significant activity in chemotherapy-naive patients with advanced ovarian cancer. Neutropenia was the dose-limiting adverse effect, whereas diarrhea was mainly mild to moderate.

[Anti-emetic effects of ondansetron hydrochloride throughout courses of cytotoxic chemotherapy].

Since the emesis induced by cytotoxic drugs is intractable, and is a possible determinant of a patient's QOL during chemotherapy, the control of this adverse event is essential to complete a course of cancer chemotherapy. The anti-emetic effects of a 5-HT3 antagonist, ondansetron hydrochloride (OND), was evaluated during a course of CDDP-containing chemotherapy. Forty-eight patients with gynecologic carcinoma, respiratory malignancy, or urological cancer were followed throughout their treatment courses. For acute emesis, prophylactic OND was given intravenously before CDDP administration, and OND tablets were used for 4 days from the day following CDDP administration as a measure against delayed emesis. The efficacy of OND gradually decreased for the acute emesis (1st course: 73.8%, 2nd course: 62.8% and 3rd course: 56.7%). The efficacy, however, did not decrease against the delayed emesis. Of patients with a good response, "effective" or "highly effective", in the previous treatment course, over 80% could again obtain a good response in the next treatment course. Adverse events of this anti-emetic treatment were not observed except for mild leukocytosis in one case, and this unexplainable effect abated without any specific treatments. In conclusion, the anti-emetic effects of OND sufficiently prevented the emetogenic action of CDDP throughout the treatment course, with a special importance for successful control in the first treatment course. The additional use of corticosteroid might enhance the effects of OND for female patients.