Irinotecan (CPT-11) and cisplatin are singly active against cervical cancer. We evaluated the efficacy and toxicity of CPT-11 plus cisplatin as first-line chemotherapy in patients with advanced or ...recurrent cervical cancer. Twenty-nine chemotherapy-naive patients with advanced or recurrent cervical cancer were treated with CPT-11 (60 mg/m(2)) on days 1, 8, and 15 by intravenous infusion over 90 min, followed by cisplatin (60 mg/m(2) i.v.) on day 1 over 90 min. The patients' median age was 57 years (range 35-75). Nineteen patients (66%) had advanced primary disease. Six patients with recurrent disease (21%) had been treated with prior radiotherapy. The remaining 4 patients (14%) had residual or recurrent disease after radical surgery. The histologic diagnoses were squamous cell carcinoma in 25 patients (87%), adenocarcinoma in 3, and adenosquamous cell carcinoma in 1. All eligible patients were included in the toxicity and response analysis based on the intent to treat. Two patients (7%) achieved a complete response and 15 (52%) a partial response (overall response rate: 59%, 95% confidence interval; 41-74%). Stable disease was recorded in 6 patients (21%) and progressive disease in 3 patients (10%). In 3 patients, image-guided evaluation of response was judged to be unfeasible at the time of independent extramural review (10%). The median time to response was 32 days (range 16-62 days). The median survival was 27. 7+ months (range, 6.4-52.8+ months). Two dose-limiting side effects were observed: grade 3 (28%) or 4 (45%) neutropenia and grade 3 (7%) or 4 (7%) diarrhea. Other severe toxicities included anemia (45%), thrombocytopenia (3%), nausea/vomiting (31%), and alopecia (7%). The combination of CPT-11 with cisplatin is an active regimen for treatment of advanced or recurrent cervical cancer albeit with a significant degree of myelosuppression.
Because it has been suggested that an environmental factor may play a role in the etiology of ovarian cancer, a case‐control study was conducted to assess some environmental and other risk factors ...for ovarian cancer from 1994 to 1996 in northern Kyushu, Japan. We analyzed the data of 89 cases with epithelial ovarian cancer and 323 controls without any cancer or ovarian disorder. After controlling for the effect of potential confounders, the odds ratios of ovarian cancer across increasing quartiles of the heaviest body weight were 1.00, 1.15, 1.71, 2.29 (P=0.008, test for trend). Significantly increased risks were noted for a history of diabetes mellitus (P<0.05), and for a family history of ovarian cancer (P<0.05). Significantly decreased trends for risk were obtained for the number of pregnancies (P<0.01) and the number of live births (P<0.001). This study provides additional support for an association between obesity and the risk of ovarian cancer. This relationship may at least partly explain the recent increase in the incidence of ovarian cancer in Japan, although possible contributions of other factors can not be ruled out.
Atypical polypoid adenomyoma (APA) most frequently presents as an endometrial polyp in premenopausal women and is believed to follow a benign course. In hysterectomy specimens from postmenopausal ...Japanease women, the endometrium contained an APA with an area of endometrial adenocarcinoma. A convincing transition zone between the APA and the adenocarcinoma was seen in our cases, suggesting that APA may develop into endometrial adenocarcinoma in postmenopausal women.
Objectives.We assessed neoadjuvant intraarterial chemotherapy (NAC) followed by radical hysterectomy and/or radiotherapy in patients with locally advanced cervical cancer.
Methods.Over 5 years, 48 ...consecutive women with International Federation of Gynecology and Obstetrics stage IIb–IVa cervical cancer were enrolled. Treatment consisted of bilateral internal iliac artery infusion of cisplatin (100 mg/m2, day 1) or carboplatin (400 mg/m2, day 1) and peplomycin (20 mg/m2, day 1) for two courses separated by 3 weeks. Doxorubicin (30 mg/m2, day 1) was added for patients with adenocarcinoma. Stage III patients who responded to NAC and Stage IIb patients underwent radical hysterectomy with pelvic lymphadenectomy. Stage III patients not responding to NAC and all stage IVa patients were treated with pelvic radiotherapy.
Results.Complete response was achieved in 5 (10.4%) of 48 patients, while a partial response was noted in 32 (66.7%) and stable disease in 11 (22.9%). Of 25 patients with stage IIIb disease, 16 (64.0%) were able to undergo surgery. The 4-year disease-free survival (DFS) was 80.0% in patients with stage IIb and 62.3% in patients with stage III. In stage IIIb, the 4-year DFS in patients receiving surgery (75.2%) was higher than the DFS for those receiving radiotherapy (44.4%) (P< 0.05). Grade 3 or 4 leukopenia developed in 17 (35.4%) patients. Nausea and vomiting of grade 2 or higher occurred in 34 (70.8%). Creatinine clearance transiently decreased (≥ grade 2) in 16.6%. Patients negative for serum squamous cell carcinoma-associated antigen (SCC) responded better to NAC than to SCC-positive cases, and SCC-negative survival was significantly better than SCC-positive survival (P< 0.05).
Conclusions.Neoadjuvant intraarterial chemotherapy with platinum was safely performed, and a survival benefit followed radical surgery with or without radiotherapy after response to NAC.
To evaluate the efficacy and toxicity of a combination of irinotecan (CPT-11) and cisplatin as first-line chemotherapy in advanced ovarian cancer.
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.
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.
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.
Objective: To clarify the behavior of endometrial hyperplasia in a prospective study.
Method: Fifty‐one patients with endometrial hyperplasia were followed up for 6 months. Samples of endometrial ...tissues were taken by uterine endometrial biopsy every 4 weeks during the first 3 months and at the end of follow‐up.
Results:/ In 69% (35/51) of the patients histological picture of the endometrium became normal during the observation period. The lesions persisted in 17% (6/35) of the patients with simple hyperplasia, in 25% (1/4) of those with complex hyperplasia, in 14% (1/7) of those with simple atypical hyperplasia, and in 80% (4/5) of the patients with complex atypical hyperplasia. In the remaining 3 patients with simple hyperplasia, the lesions progressed to complex atypical hyperplasia by the end of follow‐up, after showing a normal endometrium.
Conclusion: Most cases of endometrial hyperplasia, except for complex atypical hyperplasia, disappeared spontaneously within a short period of time.
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.
We analyzed the alteration of BRCAI in DNA obtained from 83 individuals of 13 Japanese site‐specific ovarian cancer families and 6 breast‐ovarian cancer families. Six germline mutations were detected ...in 7 families, which consisted of 4 breast‐ovarian cancer and 3 site‐specific ovarian cancer families, by single‐strand conformation polymorphism analysis, followed by direct sequence determination. The mutations included three framcshifts, two nonsense mutations, and one missense mutation causing loss of a zinc‐binding motif. The frequency of loss of heterozygosity at the microsatellite markers on the BRCAI gene was 57% (8 of 14 cases) in site‐specific ovarian cancer families, and 100% (6 of 6 cases) in breast‐ovarian cancer families. All tumors of the patients carrying a mutation of BRCAI showed deletion of wild‐type alleles, implicating BRCAI as a tumor suppressor gene. Tbese results suggest tbat germline mutations of the BRCAI gene play an important role in the carcinogen‐esis of breast and/or ovarian cancer in a majority of breast‐ovarian cancer families and in some site‐specific ovarian cancer families.
Objective: We examined uterine tissue samples obtained from premenopausal women with uterine leiomyoma treated with gonadotropin-releasing hormone agonist (GnRHa) to investigate the mechanism of the ...effects of GnRHa.
Study design: Surgically resected myoma tissue obtained from 26 premenopausal patients with uterine leiomyoma treated with GnRHa, 20 premenopausal patients with uterine leiomyoma who did not receive GnRHa treatment, and 15 postmenopausal women with uterine leiomyoma were examined histologically.
Results: GnRHa treatment reduced the size of uterine leiomyomata and induced significant hyaline degeneration in tumor tissue. Le
y
-antigen expression was detected in 18 (69.3%) of 26 GnRHa-treated patients (
P < 0.02) and in 12 (80.0%) of 15 postmenopausal women (
P < 0.05), but in only eight (40.0%) of the 20 premenopausal patients who did not receive GnRHa. Apoptotic cells, detected by the nick-end labeling method were observed in 14 patients (53.8%) in the GnRHa-treated group, 10 patients (50.0%) in the non-treated group, and 12 postmenopausal women (80.0%).
Conclusion: Our findings suggest that induction of apoptosis may be a mechanism of the effect of GnRHa in leiomyoma.
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