Docetaxel/irinotecan combination chemotherapy in platinum/taxane-refractory and -resistant ovarian cancer: JGOG/WJGOG Intergroup Study.

BACKGROUND: The aim of this phase II study was to evaluate the efficacy and toxicity of docetaxel and irinotecan combination chemotherapy in patients with ovarian cancer refractory and resistant to both platinum and taxan treatment. PATIENTS AND METHODS: Patients who had been treated with platinum and paclitaxel but whose ovarian cancer progressed or recurred within 6 months of treatment (n = 41) received docetaxel 60 mg/m(2) (day 1) and irinotecan 60 mg/m(2) (days 1, 8), repeated every 21 days [Japan Gynecologic Oncology Group (JGOG) study 3015] or every 28 days [West Japan Gynecologic Oncology Group (WJGOG) study 002] until disease progression was observed or unacceptable toxicity. Sixteen patients had platinum/paclitaxel-refractory disease, and 25 patients had platinum/paclitaxel-resistant disease. RESULTS: Thirty-two patients were available for determination of the clinical response. The overall response rate [complete response (CR) + partial response (PR)] was 6.3%, and the disease control rate (CR + PR + stable disease) was 34.4%. Among the 23 patients with resistant tumor, the disease control rate was 47.8%. Ten patients with refractory tumor showed a 10% disease control rate. The median progression-free interval was 12.1 weeks and the median overall survival time was 45.3 weeks. The major toxic adverse effect was neutropenia (grade 4, 56.1%), but the incidence of neutropenic fever was less frequent (4.9%). Neurotoxicity and gastro-intestinal toxicity were mild. CONCLUSION: Among our patients, a combination of docetaxel and irinotecan was well tolerated. However, this combination may not be a beneficial option for patients with platinum-refractory and -resistant ovarian cancer in terms of response rate and survival.

Histological grading of ovarian clear cell adenocarcinoma: proposal for a simple and reproducible grouping system based on tumor growth architecture.

In this study, we aimed to develop a histological grading system for ovarian clear cell adenocarcinoma (CCA), based on the tumor growth architectures. Cases were defined as Group A if ≥90% of a tumor examined was composed of well-differentiated tubulocystic and/or papillary architectures; Group C if at least 10% of the tumor was composed of very poorly differentiated histology (i.e. solid masses or individual infiltrating tumor cells with no or little glandular/papillary differentiation); and tumors not corresponding to the first 2 descriptions were defined as Group B. The interobserver reproducibility and prognostic value of the assigned groups were analyzed for 159 CCAs from 5 institutions. The level of agreement in assigning the groups between 2 pathologists was 88.7% (=0.82). After consensus was reached, 46 (29%), 79 (50%), and 34 (21%) tumors were classified in Groups A, B, and C, respectively. In early-stage cases [International Federation of Gynecology and Obstetrics (FIGO) stage I-II], Group A tumors had significantly better outcomes (100% 5-yr survival) than Group B tumors (82% 5-yr survival, P=0.024 by log-rank test) or Group C tumors (56% 5-yr survival, P=0.00054 by log-rank test). Moreover, early-stage Group B tumors had significantly better outcomes than Group C tumors (P<0.001 by a generalized Wilcoxon test). In advanced cases (FIGO stage III-IV), Group A tumors had significantly better outcomes than Group C tumors (52% vs. 16% 5-yr survival, respectively, P=0.043). Group A and C tumors defined with our system were identified to have favorable and unfavorable prognostic factors, respectively, independent of the clinical stage of the disease and presence of residual tumors after the initial surgery. The proposed grouping system could divide patients with CCA into 3 subgroups with distinct prognostic indications, providing a 3-tier histological grading system for ovarian CCA.

Clear cell adenocarcinoma with a component of poorly differentiated histology: a poor prognostic subgroup of ovarian clear cell adenocarcinoma.

In this study, we aimed to determine whether the presence of poorly differentiated histologic components in ovarian clear cell adenocarcinoma (CCA) affects patient prognosis. Pathologic slides from 159 patients with CCA were studied, and the tumors were classified as Por(+) in the event of poorly differentiated histology; that is, if solid masses or cords, or individual infiltrating tumor cells with little or no glandular/papillary differentiation were present in >5% of the tumor area examined. All other tumors were classified as Por(-). The prognostic value and interobserver reproducibility of this assignment were analyzed. The agreement level in the assignment between 2 pathologists was 93.7% (κ=0.86). After a consensus was reached, 53 (33%) and 106 (67%) tumors were classified as Por(+) and Por(-), respectively. Patients with Por(+) tumors showed a significantly worse outcome than those with Por(-) tumors, both in the early stages (stages I/II, 5-year survival rate 53.9% vs. 96.3%, P<0.0001 by log-rank test) and advanced stages (stages III/IV, 5-year survival rate 26.5% vs. 49.2%, P<0.001 by generalized Wilcoxon test). Por(-) tumors showed an effective response to postoperative platinum-based first-line chemotherapy more frequently compared with Por(+) tumors (48% vs. 14%, P=0.042). The Por(+) tumor was found to be an independent prognostic factor for survival irrespective of the clinical stage or presence of residual tumor after the initial surgery. These results suggest that the tumor with a poorly differentiated histology is an adverse prognostic subgroup in ovarian CCA. On the basis of the prognostic impact and interobserver reproducibility, the present binary classification system for CCAs was deemed to be highly superior to the compared conventional histologic grading system.

Validation of the histologic grading for ovarian clear cell adenocarcinoma: a retrospective multi-institutional study by the Japan Clear Cell Carcinoma Study Group.

Pathologic slides from 150 patients with clear cell adenocarcinoma from the collaborating institutions were reviewed independently by 2 pathologists, and each tumor was graded histologically using the Shimizu-Silverberg and International Federation of Gynecology and Obstetrics (FIGO) grading systems. For the Shimizu-Silverberg grading system, 3 parameters-architectural pattern, nuclear pleomorphism, and mitotic activity-were assessed and scored as 1 to 3. When the summed scores of these parameters were 3 to 5, 6 to 7, and 8 to 9, grades 1, 2, and 3 were assigned, respectively. The FIGO grade was based on the ratio of glandular/papillary growth versus solid growth: grade 1, less than 5% solid tumor; grade 2, 5% to 50% solid tumor; grade 3, greater than 50% solid tumor. Interobserver agreement levels for assignment of both gradings were fair (κ=0.32 and 0.24, respectively). After consensus had been acquired, 82 (55%), 56 (37%), and 12 (8%) tumors were classified as grades 1, 2, and 3 by the Shimizu-Silverberg grading system, and 88 (59%), 38 (25%), and 24 (16%) were classified as grades 1, 2, and 3 by the FIGO grading system, respectively. Survival analyses indicated that patients with grade 3 tumors, as defined by both the grading systems, tended to have a poor outcome, but any differences between them were not statistically significant. Multivariate analysis showed that only the presence of residual tumor after initial surgery was an independent prognostic factor for overall survival. These results suggest that the 2 tested grading systems have limited value for the prognostication of patients with clear cell adenocarcinoma, and that a more effective grading system for this tumor may be required.

Less impact of adjuvant chemotherapy for stage I clear cell carcinoma of the ovary: a retrospective Japan Clear Cell Carcinoma Study.

INTRODUCTION: Ovarian clear cell carcinoma (CCC) is regarded as grade 3 tumor, and the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines recommend adjuvant chemotherapy for the tumor even at stage IA. However, CCC often showed chemo-resistant phenotype, and the effect of adjuvant chemotherapy still remained uncertain. METHODS: Clear cell carcinoma cases treated at collaborating institutions during the period 1992-2005 were retrospectively identified. After a central pathological review, survival analysis was estimated by the Kaplan-Meier method, and prognostic factors were evaluated using a Cox regression model. RESULTS: Among 219 patients with stage I CCC, 195 patients received adjuvant chemotherapy (C+) and 24 patients (C-) did not. The C+ group had 77 pT1a and 118 pT1c cases, and the C- group included 18 pT1a and 6 pT1c tumors (P < 0.001). The median age was 52 years in the C+ group and 57 years in C- group (P = 0.04). During the median follow-up period of 48 months (range, 7-160 years), relapse was observed in one patient (4%) in the C- group and in 35 patients (18%) in the C+ group. There were no statistical differences of progression-free survival and overall survival between the C+ and the C- groups. Multivariate analysis revealed that peritoneal cytology status (P = 0.02) and pT status (P = 0.04) were independent prognostic factors for progression-free survival; however, adjuvant chemotherapy was not a prognostic factor (P = 0.80). CONCLUSIONS: Although the present study was a limited retrospective investigation, it suggested that adjuvant chemotherapy had little impact on the survival of stage I CCC patients. Further strategy, such as a molecular targeting agent, is needed to improve survival of CCC, especially in cases with positive peritoneal washing.

The impact of complete surgical staging upon survival in early-stage ovarian clear cell carcinoma: a multi-institutional retrospective study.

Pure-type clear cell carcinoma (CCC) has been recognized as a distinct subtype of ovarian cancer, showing resistance to conventional platinum-based chemotherapy and resulting in poor prognosis. The aim of the study was to evaluate the effects of complete surgical staging procedures for early-stage CCC patients in a retrospective multi-institutional analysis. During the period 1992 to 2002, a total of 199 patients with pT1 M0 CCC were identified. Survival analysis was estimated by Kaplan-Meier methods, and prognostic factors were evaluated using a Cox regression model. Among pT1 M0 tumors, retroperitoneal lymph node status was negative in 125 cases (pN0, 63%), positive in 10 cases (pN1, 5%), and unknown in 64 cases (pNx, 32%). Progression-free survival of pN1 was significantly worse than that of pN0 (P < 0.05), whereas there was no significant difference between pN1 and pNx. There was no significant difference of overall survival (OS) among the 3 groups. Multivariate analysis revealed that peritoneal cytology status was the only independent prognostic factor for progression-free survival (P = 0.04), but completion of surgical staging procedures was not a prognostic factor. There was no significant prognostic factor for OS. Our study implied that complete surgical staging enabled us to distinguish a high-risk group of recurrence in pT1 M0 CCC; however, the procedure could not improve OS. Although the study was a limited retrospective study, the impact of peritoneal cytology status was more important than complete surgical staging procedure in CCC patients. More effective treatment modality was warranted, especially for CCC cases positive for malignant peritoneal cytology.

Progression-free survival and overall survival of patients with clear cell carcinoma of the ovary treated with paclitaxel-carboplatin or irinotecan-cisplatin: retrospective analysis.

BACKGROUND: Irinotecan hydrochloride, a topoisomerase I inhibitor, has been preliminarily recognized as an effective agent against clear cell carcinoma of the ovary (CCC), but there are few clinical data. Our aim was to compare progression-free survival (PFS) between patients treated with irinotecan hydrochloride and cisplatin (CPT-P) and those with treated with paclitaxel and carboplatin (TC). METHODS: One hundred and seventeen patients at International Federation of Gynecology and Obstetrics (FIGO) stages Ic (ascites/malignant washing) - IV were identified by scanning the medical records of ten Japanese hospitals. After complete surgical staging procedures including lymphadenectomy, 35 patients received CPT-P and 82 patients received TC. The PFS and overall survival of the two groups were compared using the Kaplan-Meier method. RESULTS: There was no significant difference in median age, performance status, FIGO stage, rate of optimal cytoreduction, or follow-up period between the CPT-P and TC groups. Two-year and 5-year PFS was 48% and 40%, respectively, in the TC group and 55% and 55%, respectively, in the CPT-P group (P = 0.31). Multiple regression analysis revealed that only residual tumor was an independent prognostic factor for PFS (P < 0.01). CONCLUSION: CPT-P showed a potential therapeutic effect, at least no less than that of TC therapy. Although there was no significant survival benefit in the present retrospective analysis, we recommend that the CPT-P regimen be evaluated in a larger, prospective, clinical trial.

Adjuvant chemotherapy with irinotecan hydrochloride and cisplatin for clear cell carcinoma of the ovary.

Clear cell carcinoma (CCC) of the ovary has distinct characteristics showing resistance to conventional platinum-based regimen. Our aim was to evaluate the effects of combination therapy with irinotecan hydrochloride and cisplatin (CPT-P), comparing to regimen with paclitaxel and platinum (TP). We retrospective reviewed 172 patients with complete surgical staging procedures including lymphadenenctomy. Forty-six patients received CPT-P and 126 patients were treated with TP. Survival of the two groups was compared. Between CPT-P group and TP group, there was no significant difference in median age, performance status, FIGO stage, rate of optimal cytoreduction, and follow-up period. There was no significant difference in progression-free survival of patients with stage I tumors (p=0.95) and suboptimally debulked stage II-IV tumors (p=0.92). Although there was no significant difference of overall survival, progression-free survival of CPT-P group was significantly better than that of TP group in optimally debulked stage II-IV (p=0.03). Multiple regression survival analysis revealed CPT-P regimen (p=0.02) and residual tumor diameter (p<0.01) were both independent prognostic factors in stage II-IV tumors. The combination of CPT-P was shown to have a potential therapeutic benefit for advanced CCC of the ovary, especially for cases with optimal debulking surgery. However, this is a limited retrospective study, therefore we recommend that the CPT-P regimen be evaluated in a larger prospective study.

Ovarian metastasis in carcinoma of the uterine cervix.

BACKGROUND: The present study was conducted to determine the frequency and clinicopathological features of ovarian metastasis in a large population of patients with stage Ib-IIb cervical cancer. METHODS: The study population consisted of 3471 patients with stage Ib to IIb cervical cancer who underwent radical hysterectomy, including pelvic lymphadenectomy and bilateral salpingo-oophorectomy, at our six institutions between 1981 and 2000. To our knowledge, this study is the largest review of patients with ovarian metastasis from cervical cancer. We reviewed the patients' medical records to determine clinicopathological features. RESULTS: Fifty-two patients (1.50%) had ovarian metastases: 6 in stage Ib1, 12 in stage Ib2, 5 in stage IIa, and 29 in stage IIb. The mean age of patients with ovarian metastasis was 49.9 years (range: 29-73 years). The incidence of ovarian metastasis in patients with cervical cancer was 0.22% for stage Ib, 0.75% for stage IIa, and 2.17% for stage IIb with squamous cell carcinoma, and 3.72%, 5.26%, and 9.85%, respectively, in adenocarcinoma. Ovarian metastasis occurred more frequently among patients with adenocarcinoma than among those with squamous cell carcinoma (5.31% vs. 0.79%). Outcome for patients with ovarian metastasis was very poor and not related to FIGO stage and histological type. The presence of ovarian metastasis did not correlate with lymph node involvement or parametrial invasion. CONCLUSION: Study results indicate that ovaries can be preserved in patients with stage Ib-IIa squamous cell carcinoma but removed in all patients with adenocarcinoma.

[Endometrial cancer].

The current treatment of choice for endometrial cancer is reported to be primary surgery including a total abdominal hysterectomy, bilateral salpingo-oophorectomy, peritoneal cytologic sampling, and exploration, palpation, and biopsy of any suspicious lymph nodes or lesions. This allows determination of the extent of the disease, the stage of malignancy and the risk of recurrence. Adjuvant radiation therapy is administered to the pelvis for intermediate-risk patients, and a systemic chemotherapy is considered for high-risk ones, while no treatment is added for low-risk patients. But for patients with the malignancy, many Japanese gynecologists have performed extended hysterectomy instead of total hysterectomy to reduce the incidence of vaginal recurrence, achieved the pelvic and para-aortic lymphadenectomy as a substitute for biopsy sampling to avoid recurrence in lymph nodes, and given cytotoxic chemotherapy in place of irradiation to prevent radiation morbidity and recurrence at a distant site. Although differences in treatments for advanced disease have disappeared, further efforts are recommended to find useful prognostic factors for distinguishing patients with poorer prognoses, and to establish a standard treatment for endometrial cancer all over the world.

Association of XRCC1 Arg399Gln and OGG1 Ser326Cys polymorphisms with the risk of cervical cancer in Japanese subjects.

OBJECTIVE: In this study, genetic polymorphisms, XRCC1 Arg399Gln and OGG1 Ser326Cys were examined with reference to cervical cancer risk in a population-based incident case-control study in Japan. METHODS: The cases comprised 131 cervical cancer patients: 87 cases with squamous cell carcinoma (SCC) and 44 with adenocarcinoma (ADC) or adenosquamous carcinoma (ADSC). Controls were sampled from 320 healthy women who underwent a health checkup. RESULTS: The frequency of the XRCC1 399GlnGln genotype was higher in individuals with adenocarcinoma/adenosquamous carcinoma than in the healthy controls (OR = 2.98, 95% CI = 1.11-8.01, P = 0.030). However, no association was demonstrated in SCC. Analysis of OGG1 Ser326Cys polymorphism showed no significant differences between cervical cancer patients and controls. In stratification analysis, significant elevated risk of adenocarcinoma/adenosquamous carcinoma was associated with the XRCC1 399GlnGln genotype among nonsmokers (OR = 3.85, 95% CI = 1.28-11.59, P = 0.017), but not among smokers. No gene-gene interaction was observed in our case subjects. CONCLUSION: This is the first report that the XRCC1 Arg399Gln polymorphism might be important in relation to the risk of adenocarcinoma/adenosquamous carcinoma of the cervix.

[A dose escalation study of concurrent chemoradiation therapy with nedaplatin for cervical cancer].

Doses of nedaplatin (CDGP) were established for concurrent chemoradiation therapy (CCRT) for cervical cancer, and a collaborative dose escalation study involving 8 hospitals was conducted to investigate the safety and efficacy of this therapy. Radiotherapy was performed according to the standard treatment described in the Regulations of Cervical Carcinoma Treatment. CDGP at 80 mg/m2 as Level 1 or at 90 mg/m2 as Level 2 was administered on Days 1 and 29 of treatment. Dose-limiting toxicity (DLT) was observed in 1 of 6.patients receiving 80 mg/m2 of CDGP and in all 2 patients receiving 90 mg/m2 of CDGP; therefore, Level 2 was regarded as the maximum tolerated dose (MTD), and Level 1 as the recommended dose. DLT signs consisted of delayed improvement in the leukocyte count in 2 patients and anorexia in 1 patient, suggesting that delayed improvement in the leukocyte count is the main DLT of this combination therapy. The main side effects were digestive disorders such as nausea and anorexia and bone marrow suppression, such as leukopenia, neutropenia, and thrombopenia. Side effects in the Level 1 group were more mild than in the Level 2 group. The efficacy was PR or better in all patients. The CR rates were 60% (6/10) in the Level 1 group and 50% (1/2) in the Level 2 group; there was no marked difference between the two groups. These results suggest that CCRT involving administration of CDGP at 80 mg/m2 on Days 1 and 29 is safe and effective.

Association of p73 G4C14-to-A4T14 polymorphism at exon 2 and p53 Arg72Pro polymorphism with the risk of endometrial cancer in Japanese subjects.

To test the association of endometrial cancer with the p73 G4C14-to-A4T14 polymorphism in exon 2 and the p53 Arg72Pro polymorphism, an incident case-control study was performed in Japanese subjects. The cases comprised 114 endometrial cancer patients, and the controls were 320 healthy females and 122 noncancer female outpatients. An unconditional logistic regression model demonstrated a significant association between the p73 AA genotype and an increased risk of endometrial cancer (OR=2.82, 95% CI=1.36-5.82), especially of type-I tumors (OR=3.24, 95% CI=1.53-6.87). In contrast, there was no significant difference in the p53 Arg72Pro genotype frequency between the controls and cases.

Association of the NAD(P)H: quinone oxidoreductase C609T polymorphism and the risk of cervical cancer in Japanese subjects.

OBJECTIVE: In this study, genetic polymorphisms, NQO1 C609T, GSTM1 positive/null, and GSTT1 positive/null, were examined with reference to cervical cancer risk in a population-based incident case-control study in Japanese. METHODS: The cases comprised 131 cervical cancer patients: 87 cases with squamous cell carcinoma (SCC) and 44 with adenocarcinoma (ADC) or adenosquamous carcinoma (ADSC). Controls were sampled from 320 healthy women who underwent a health checkup. RESULTS: The cervical cancer risk was substantially elevated with smoking for all cases, SCC cases, and ADC/ADSC cases (OR = 4.50, 95% CI = 2.48-8.17, P < 0.001; OR = 5.68, 95% CI = 2.99-10.78, P < 0.001; and OR = 2.57, 95% CI = 1.09-6.08, P = 0.032; respectively). The frequency of the NQO1 609TT genotype, reported to be associated with null enzyme activity, was higher in individuals with all cases and SCC than in the healthy controls (OR = 1.97, 95% CI = 1.06-3.66, P = 0.032; and OR = 2.42, 95% CI = 1.21-4.82, P = 0.012; respectively), but not in ADC/ADSC cases. Analysis of polymorphisms for GSTM1 and GSTT1 showed no significant differences between cervical cancer patients and controls. In stratification analysis, significant elevated risk of all cases and SCC was associated with the NQO1 609TT genotype among nonsmokers (OR = 2.15, 95% CI = 1.08-4.30, P = 0.030; and OR = 2.83, 95% CI = 1.21-6.31, P = 0.011; respectively), but not smokers. No gene-gene interaction was observed in our case subjects. CONCLUSION: This is the first report that the NQO1 gene might be important in relation to the risk of squamous cell carcinoma of the cervix.

Lymphotoxin-alpha polymorphism and the risk of cervical cancer in Japanese subjects.

To examine the possible association between cervical cancer and Lymphotoxin-alpha (LT(alpha)) polymorphisms, C804A and A252G, an incident case-control study was conducted in Japanese. The cases were 131 cervical cancer patients. Controls were 320 healthy women. Risk estimation was conducted by an unconditional logistic model. Complete linkage disequilibrium was seen between LT(alpha) C804A and LT(alpha) A252G. We found that, compared with the 804CC genotype, 804CA and 804AA were associated with a decreased risk of cervical cancer (OR = 0.64, 95% CI = 0.40-1.02; and OR = 0.45, 95% CI = 0.21-0.95, respectively), especially of SCC (OR = 0.54, 95% CI = 0.32-0.91; and OR = 0.39, 95% CI = 0.16-0.92, respectively).

Chemoradiotherapy for uterine cancer: current status and perspectives.

The conventional local treatment methods (surgery and radiation) for cervical cancer have reached a plateau in terms of survival benefit and, therefore, in this review, new treatment strategies (combined chemotherapy [CT] and local therapy) to overcome the poor prognosis were examined in high-risk groups. The effectiveness of neoadjuvant chemotherapy (NAC) administered prior to radiotherapy (RT) has not been confirmed for any disease stages. But NAC followed by surgery may improve survival in patients with stage Ib2 compared with surgery alone; and in patients with stage Ib2 to IIB compared with RT alone. Five large randomized clinical trials (RCTs) demonstrated a significant survival benefit for patients treated with concurrent chemoradiotherapy (CCRT), using a cisplatin (CDDP)-based regimen, with a 28%-50% relative reduction in the risk of death. In addition, the results of a metaanalysis of 19 RCTs of CCRT (1981-2000) involving 4580 patients showed that CCRT significantly improved overall survival (OS) hazard ratio ([HR] 0.71; P < 0.0001), as well as progression-free survival (PFS; HR 0.61; P < 0.0001). In line with these results, CCRT is currently recommended as standard therapy for advanced cancer (stage III/IVA) in the United States. However, there remains much controversy and uncertainty regarding the optimal therapeutic approaches, especially for patients with advanced cancer. Additional RCTs should be conducted to find the optimal CT regimen and RT for Japanese patients, considering acute and late complications, as well as differences in pelvic anatomy, total radiation dose, and RT procedures between Japan and other countries. Evidence obtained from such studies should establish the optimal CCRT treatment protocol and define the patient population (disease stage) that the protocol really benefits.

Phase II trial of 3-h infusion of paclitaxel in patients with adenocarcinoma of endometrium: Japanese Multicenter Study Group.

OBJECTIVE: We assessed the antineoplastic effect and adverse reactions of paclitaxel monotherapy with paclitaxel 210 mg/m(2) given every 3 weeks by 3-h infusion on patients with endometrial cancer given as a 3-h infusion. METHODS: This study was a multi-center, open-label phase II clinical trial of paclitaxel 210 mg/m(2) given every 3 weeks by 3-h infusion. Patients with advanced or recurrent endometrial cancer were enrolled. The primary endpoint for efficacy was tumor response rate. The secondary endpoints were duration of response and adverse drug reactions. RESULTS: Among 23 patients evaluated for efficacy, partial remission (PR) was achieved in 7, no change (NC) in 10, progressive disease (PD) in 5, and not estimable (NE) in 1. The overall response rate was 30.4% (7/23 cases). In seven PR cases, median duration of response was 130 days (100-245 days). Subjective or objective symptoms > or =grade 3 included febrile neutropenia and constipation in 8.7% (2/23 cases) each; and nausea, vomiting, fatigue, pain, urinary tract infection, lowered oxygen saturation, anorexia, arthralgia, myalgia, neuropathy, weight loss, dyspnea, and need for red cell transfusion in 4.3% (1/23) each. Laboratory test abnormalities > or =grade 3 included neutropenia (78.3%, 18/23), leucopenia (47.8%, 11/23), lowered hemoglobin (13.0%, 3/23), decreased potassium (8.7%, 2/23), and decreased sodium (4.3%, 1/23). All adverse reactions were successfully managed by prolonging treatment interval, dose reduction, interrupting administration, discontinuation, and administration of G-CSF. CONCLUSION: Three-hour intravenous infusion of paclitaxel 210 mg/m(2) is useful for endometrial cancer. Antineoplastic effect was achieved and adverse reactions were clinically manageable.

[Endocrine tumor of the uterine cervix].

Endocrine tumor of the uterine cervix is rare, as only nine cases have been reported as patients who troubled by the ectopically endocrine hormone. Five of these patients afflicted by ectopic ACTH secretion which caused Cushing's syndrome, two suffered by insulin which resulted hypoglycemia, one distressed by PTH, and the other troubled by G-CSF. Seven of the nine patients were diagnosed histologically as small cell carcinoma, which was famous for neuroendocrine tumor, high incidence of vascular invasion and lymph node involvement, clinical behavior of hematogenously dissemination, and poor prognosis. Age of six patients was less than 50 years old, and metastatic tumor was confirmed in six of the nine patients.