Cervical, endometrial, and ovarian cancers, have both high morbidity and mortality among the gynecologic malignant tumors in Japan. The present study was conducted using both the population-based cancer registry and the gynecologic cancer registry to elucidate the characteristics of gynecologic malignant tumors in Japan. Based on nationwide estimates from the population-based cancer registry in Japan, the morbidities and mortality of cervical, endometrial, and ovarian cancers were obtained and used for analysis. Clinicopathologic factors for cervical cancer, endometrial cancer, ovarian cancer, including age, clinical stage, postsurgical stage, histological type, therapeutic strategy, and prognosis were retrieved from the gynecologic cancer registry published by the Japan Society of Obstetrics and Gynecology and used for analysis. The morbidities of cervical, endometrial, and ovarian cancers were 10,908, 13,606, and 9,384 women in 2012, respectively. The prevalence of endometrial cancer has significantly and consistently been increasing and represents the most common gynecologic malignant tumor in Japan. The mortalities of cervical, endometrial, and ovarian cancers were 2.1, 1.3, and 3.2 per 100,000 in 2012, respectively. In 2014, 52.2% of cervical cancer patients were classified as stage I, 22.5% as stage II, 10.2% as stage III, and 11.2% as stage IV. In addition, 71.9% of endometrial cancer patients were classified as stage I, 6.0% as stage II, 13.3% as stage III, and 7.5% as stage IV. Finally, 43.2% of ovarian cancer patients were classified as stage I, 9.1% as stage II, 27.6% as stage III, and 7.2% as stage IV. Twelve point five percent of ovarian cancer patients received neoadjuvant chemotherapy.
Drug Therapy ; Endometrial Neoplasms ; Female ; Genital Neoplasms, Female ; Gynecology ; Humans ; Japan* ; Mortality ; Obstetrics ; Ovarian Neoplasms ; Prevalence ; Prognosis ; Registries ; Uterine Cervical Neoplasms

Bevacizumab is increasingly used in recurrent, persistent or metastatic cervical cancer. The early retrospective case reports found that bevacizumab combined with 5-FU (including capecitabine) or paclitaxel was well tolerated and displayed encouraging anti-tumor activity in recurrent or persistent cervical cancer. Phase Ⅱ clinical trials showed that bevacizumab was well tolerated and active in the second- and third-line treatment of patients with recurrent cervical cancer. Large scale phase Ⅱ and phase Ⅲ clinical trials demonstrated that bevacizumab-containing chemotherapy was effective in the first- and second-line treatment of patients with persistent cervical cancer, prolonged survival time and improved remission rate. The article also reviews the research progress on predictive factors of bevacizumab efficacy, showing the use of imaging and biomarkers in predicting the efficacy of bevacizumab treatment. In addition, this article analyzes the cost-effectiveness of bevacizumab, finding that bevacizumab combined with chemotherapy meets the standard of cost-effectiveness.
Antineoplastic Combined Chemotherapy Protocols ; economics ; therapeutic use ; Bevacizumab ; economics ; therapeutic use ; Cost-Benefit Analysis ; Female ; Fluorouracil ; economics ; therapeutic use ; Health Care Costs ; Humans ; Neoplasm Recurrence, Local ; drug therapy ; Paclitaxel ; economics ; therapeutic use ; Remission Induction ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Uterine Cervical Neoplasms ; drug therapy ; economics ; mortality

OBJECTIVE: The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. METHODS: This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. RESULTS: In the UFT group, 103 patients (63.6%) received UFT for > or =90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). CONCLUSION: High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease.
Administration, Oral ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Retrospective Studies ; Tegafur/administration & dosage/adverse effects ; Treatment Outcome ; Uracil/administration & dosage/adverse effects ; Uterine Cervical Neoplasms/*drug therapy/mortality

OBJECTIVE: To evaluate the efficacy and tolerability of a neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy in patients with locally advanced cervical carcinoma. METHODS: Patients with histologically confirmed locally advanced cervical carcinoma, aged > or =18 years, were treated with intravenous ifosfamide 5,000 mg/m2 and mesna 5,000 mg/m2, on day 1; intravenous paclitaxel 175 mg/m2 and cisplatin 75 mg/m2, on day 2; every 3 weeks for three cycles. Following chemotherapy, operable patients underwent radical hysterectomy and pelvic lymphadenectomy, and, if necessary, adjuvant radiotherapy. RESULTS: One hundred fifty-two patients with median age 53 years (range, 24 to 79 years), FIGO stage IIB in 126 (89%), were treated with chemotherapy for median 3 cycles (range, 1 to 3). Treatment was delayed or withdrawn in 23 patients (15%). One hundred thirty-nine patients (91%) underwent surgery. Postchemotherapy pathological complete response rate was 18% (25 patients). Postoperative radiotherapy was administered in 100 patients (72%). The 5-year overall survival and progression-free survival were 87.3% (95% confidence interval [CI], 84.5 to 90.3) and 76.4% (95% CI, 73.5 to 79.5), respectively. CONCLUSION: Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy was feasible and effective in the treatment of locally advanced cervical carcinoma patients with older age and more advanced disease stage than reported in previous studies. Hematological and renal toxicity could be carefully prevented.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carcinoma, Squamous Cell/*drug therapy/mortality/pathology ; Cisplatin/*administration & dosage/adverse effects ; Disease Progression ; Feasibility Studies ; Female ; Humans ; Ifosfamide/*administration & dosage/adverse effects ; Middle Aged ; Neoadjuvant Therapy ; Paclitaxel/*administration & dosage/adverse effects ; Retrospective Studies ; Treatment Outcome ; Uterine Cervical Neoplasms/*drug therapy/mortality/pathology ; Young Adult

OBJECTIVE: The concept of platinum sensitivity and cross-resistance among platinum agents are widely known in the management of recurrent ovarian cancer. The aim of this study was to evaluate two hypotheses regarding the validity of the concept of platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer. METHODS: In this retrospective study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving cisplatin based chemotherapy (including concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line chemotherapy at the time of recurrence between April 2004 and July 2012 were reviewed. RESULTS: In total, 49 patients-34 squamous cell carcinomas (69.4%) and 15 non-squamous cell carcinomas (30.6%)-were enrolled. The median age was 53 years (range, 26 to 79 years). Univariate and multivariate analysis showed that a platinum free interval (PFI) of 12 months has a strong relationship with the response rate to second-line chemotherapy. Upon multivariate analysis of survival after second-line platinum-based chemotherapy, a PFI of 12 months significantly influenced both progression-free survival (hazard ratio [HR], 0.349; 95% confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR, 0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6 months, the difference of progression-free survival between patients with re-administration of cisplatin (3.0 months) and administration of cisplatin analogue (7.2 months) as second-line chemotherapy was statistically significant (p=0.049, log-rank test). CONCLUSION: The concept of platinum sensitivity could be applied to recurrent cervical cancer and there is a possibility of noncross-resistance of cisplatin analogue with cisplatin.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Carboplatin/administration & dosage ; Carcinoma, Squamous Cell/*drug therapy/mortality ; Cisplatin/administration & dosage/*analogs & derivatives ; Drug Resistance, Neoplasm ; Female ; Humans ; Kaplan-Meier Estimate ; Middle Aged ; Neoplasm Recurrence, Local/*drug therapy ; Organoplatinum Compounds/administration & dosage ; Retreatment ; Retrospective Studies ; Treatment Outcome ; Uterine Cervical Neoplasms/*drug therapy/mortality

OBJECTIVETo investigate the effect of adjuvant chemotherapy on the prognosis of patients with low-risk cervical cancer (without pelvic lymph node metastasis, parametrial involvement, positive surgical margin, primary tumor size > 4 cm, deep cervical stromal invasion, or lymph-vascular space invasion).

METHODSThe clinical data of 208 patients with low-risk cervical cancer were studied retrospectively to analyze the indications of adjuvant chemotherapy and its relationship with tumor recurrence and the patients' survival.

RESULTSThe median follow-up time of the cohort was 73 months. The overall tumor recurrence rate was 4.8% and the total 5-year survival rate of the patients was 96.0%. Sixty-nine of the patients received adjuvant chemotherapy (Taxol+Cisplatin) after the operation with a median of 2.5 (2-4) courses. Univariate analysis showed that the histological tumor grade was significantly associated with adjuvant chemotherapy (P<0.001). In the 114 grade III patients, 50 received adjuvant chemotherapy as compared with 19 in the 94 grade I-II patients. Among the grade III patients, no significant differences was found in the overall survival rate (97.0% vs 95.0%) or tumor recurrence rate (4.0% vs 4.7%) rate between the patients with adjuvant chemotherapy and those without. The tumor size (2 cm or less vs >2 cm) was significantly associated with tumor recurrence rate (1.1% vs 7.5%, P=0.034) and the overall 5-year survival rate (100.0% vs 93.0%, P=0.034) in the 208 patients. In the 139 patients receiving only surgical treatment, the tumor recurrence and 5-year survival rates were not significantly correlated with the histologic grade, age, FIGO staging, gross type, tumor size or histologic type.

CONCLUSIONB There has been no sufficient evidence to support the prescription of postoperative adjuvant chemotherapy for low-risk cervical cancer based on histological grading of the tumor, which may not help in reducing tumor recurrence or improving the long-term survival of the postoperative patients.

Adult ; Aged ; Chemotherapy, Adjuvant ; Female ; Humans ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Uterine Cervical Neoplasms ; drug therapy ; mortality ; pathology ; Young Adult

Pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy (NAC-VBP). The aim of this study was to evaluate pulmonary toxicity related to a quick course NAC-VBP. A total of consecutive 61 patients, who underwent at most 3 cycles of NAC-VBP every 10 days in the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer from 1995 to 2007, were retrospectively analyzed. Of the 61 study subjects, 7 (11.5%) were identified to have pulmonary toxicity and 2 (3.3%) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach. No factor predisposing pulmonary toxicity was identified. Initial symptoms were non-specific, but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high-resolution computed tomography of the chest. The benefit of steroid therapy was uncertain and was associated with steroid-induced diabetes mellitus requiring insulin therapy in two patients. Fatal pulmonary toxicity is a major concern of a quick course NAC-VBP. In conclusion, these patients require special monitoring for bleomycin-induced pulmonary toxicity.
Aged ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage/*adverse effects/therapeutic use ; Bleomycin/administration & dosage/*adverse effects/therapeutic use ; Cisplatin/administration & dosage/*adverse effects/therapeutic use ; Female ; Humans ; Lung Diseases/*chemically induced/pathology ; Middle Aged ; *Neoadjuvant Therapy ; Pulmonary Fibrosis/chemically induced/mortality/pathology ; Retrospective Studies ; Tomography, X-Ray Computed ; Uterine Cervical Neoplasms/complications/*drug therapy ; Vincristine/administration & dosage/*adverse effects/therapeutic use

OBJECTIVE: To investigate the effect of neoadjuvant chemotherapy on cervical carcinoma and its association with clinical data. METHODS: A total of 97 patients with stage Ib2 approximately IIIa of cervical cancinoma were treated with neoadjuvant chemotherapy. The effect of chemotherapy, factors associated with outcome of chemotherapy, and histology were analyzed. RESULTS: Effective rate of chemotherapy was 86.6% which was associated with clinical stage and histology. Eight-four patients received radical hysterectomy. The histological grade of 17 patients was lowered, lymph nodes in 19 patients were positive, and 6 patients had parametrium invasion. One patient died within 1 year after the operation, and 5 patients recurred. CONCLUSION The effect of neoadjuvant chemotherapy for locally advanced cervical cancinoma is good. Surgery after chemotherapy can improve the prognosis and 5-year survival rate.
Adenocarcinoma ; drug therapy ; mortality ; surgery ; Adult ; Carcinoma, Squamous Cell ; drug therapy ; mortality ; surgery ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; methods ; Prognosis ; Survival Rate ; Uterine Cervical Neoplasms ; drug therapy ; mortality ; surgery

OBJECTIVE: To evaluate the outcomes of laparoscopico-vaginal (modified) radical hysterectomy and to compare surgical parameters and recurrence rate of these with those of conventional abdominal radical hysterectomy. METHODS: From October 1997 to March 2002, we have performed 37 cases of LVMRH (laparoscopico- vaginal modified radical hysterectomy) +PLND (pelvic lymph node dissection) and 47 cases of LVRH (laparoscopico-vaginal radical hysterectomy) with paraaortic lymph node sampling +PLND. Inclusion criteria for laparoscopic group were patients with FIGO stage IA1 to IB1 which exocervical mass size was less than 2 cm clinically. As a control group, we selected 46 cases for the MRH group and 96 cases for the RH group. These groups had the same FIGO stage and the same tumor size less than 2 cm or tumor volume calculated by MRI being less than 4.2 cm3, while the age for each group were identically matched with the laparoscopic group. RESULTS: The mean duration of surgery, the number of lymph nodes and the rate of perioperative and postoperative complications were similar in both the laparoscopic and the conventional laparotomy group. The mean duration of hospital stay was significantly shorter in patients treated by laparoscopic surgery (LVMRH vs. MRH; 9 vs. 15, LVRH vs. RH; 13 vs. 21 days). No lymph node metastasis was reported in both LVMRH and MRH group. No recurrences but only one patient in MRH group were found in both groups during the median follow up of 34.5 and 43.5 months, respectively. The positive rates of pelvic lymph node metastasis in both RH groups were similarly 6.4%. Four (8.5%) of 47 LVRH patients and two (2.1%) of 96 RH patients had recurrences. However, in patients who had tumor volume being less than 4.2 cm3, recurrence rate was 2.5% (1/40) and 42.9% (3/7) in those with tumor volume larger than 4.2 cm3. There was one death in a patient with pulmonary metastasis who took LVRH in spite of vigorous chemotherapy. Three year progression free survival rates were 96.7% in LVRH group (tumor volume<4.2 cm3) and 97.9% in RH group (p=0.81). CONCLUSION: Laparoscopic surgery for treatment of early small volume cervical cancer, especially stage IA is safe and effective alternatives in terms of operative morbidity and mortality. However, patients with large volume disease (>4.2 cm3) who were treated by LVRH had higher recurrence rate compared to those by conventional RH. It is concluded that laparoscopic surgery for the treatment of cervical cancer would be better to be limited to patients with early disease who have the largest tumor diameter less than 2 cm or tumor volume less than 4.2 cm3 carefully measured by MRI.
Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Humans ; Hysterectomy* ; Laparoscopy ; Laparotomy ; Length of Stay ; Lymph Nodes ; Magnetic Resonance Imaging ; Mortality ; Neoplasm Metastasis ; Postoperative Complications ; Recurrence ; Tumor Burden ; Uterine Cervical Neoplasms*

OBJECTIVE: The purpose of this study was to evaluate the efficacy and toxicity of concurrent chemor- adiotherapy (CCRT) in loco-regionally advanced cervical cancer patients. METHODS: The medical records of 24 patients were retrospectively reviewed who underwent CCRT' and 62 patients who had underwent radiation therapy alone at the Department of Obstetrics and Gynecology, Ajou University Hospital from September, 1994 to August 2000 for loco-regionally advanced cervical cancer (stage IIb-IVa and Ib-IIa with bulky tumor mass or pelvic lymph node involvement detected by magnetic resonance imaging). Radiotherapy was performed for 7 weeks during which the patients underwent radiotherapy and chemotherapy concomitantly. Chemotherapeutic regimen consisted of cisplatin (75 mg/m2 on day 1, 4) and 5-FU (1000 mg/m2 on day 2-5, 30-33). The toxicity was assessed according to the GOG toxicity criteria. RESULTS: In the CCRT group, 2 of 18 patients (11.1%) had recurrent disease. Of the 22 patients who were followed up, the overall survival rate was 83.3%, and the relapse-free survival rate was 89.9%. In the radiotherapy alone group, 19 of 61 patients (32.3%) had recurrent disease. Of the 62 patients who were followed up, the overall survival rate was 75.4% and the relapsed-free survival rate was 67.7%. Relative risk reduction rate of the death rate in the CCRT group was 66% (RR 0.34), and 32% (RR 0.68) in the recurrence rate. Acute toxicities in the CCRT group were enteritis grade 3:3 (12.5%), leukopenia grade 3:2 (8.3%), anemia grade 3:1 (4.1%) and grade 4:2 (8.3%). The acute toxicities in the radiation therapy alone group were enteritis grade 3:7 (11.3%), rectal bleeding grade 3:1 (1%). Increased acute toxicities developed in the CCRT group. CONCLUSION: This study shows improved overall survival rates and relapse-free survival rates but some increase in acute toxicity. It is suggested that CCRT be the standard treatment of loco-regionally advanced cervical cancer. Due to small size sample and short duration of follow up, further study of a large group of patients and the long term survival rate are necessary.
Anemia ; Chemoradiotherapy* ; Cisplatin ; Drug Therapy ; Enteritis ; Fluorouracil ; Follow-Up Studies ; Gynecology ; Hemorrhage ; Humans ; Leukopenia ; Lymph Nodes ; Medical Records ; Mortality ; Obstetrics ; Radiotherapy ; Recurrence ; Retrospective Studies ; Risk Reduction Behavior ; Survival Rate ; Uterine Cervical Neoplasms*