A single-institution retrospective exploratory analysis on the effectiveness and safety of lenvatinib plus pembrolizumab for advanced endometrial cancer: insights from ProMisE molecular classification system.

BACKGROUND: The Proactive Molecular Risk Classifier for Endometrial Cancer has identified four risk groups for the prognosis of endometrial cancer. Lenvatinib plus pembrolizumab was recently approved as a second-line treatment for unresectable endometrial cancer, but reports in clinical practice are lacking. The relationship between the efficacy of lenvatinib/pembrolizumab and Proactive Molecular Risk Classifier for Endometrial Cancer classification is unclear. METHODS: This single-centre retrospective study included patients who underwent lenvatinib/pembrolizumab therapy at Iwate Medical University Hospital between January 2022 and March 2023. Formalin-fixed paraffin-embedded specimens obtained from patients before treatment were collected and classified into the mismatch repair-deficient, p53 abnormal and no specific molecular profile subtypes using immunohistochemistry. The response rate, progression-free survival and adverse events were evaluated using electronic medical records. The study was approved by the hospital's ethics committee (approval number: MH2022-093). RESULTS: This study enrolled 20 patients, who underwent a median follow-up of 17.8 months (95% confidence interval: 16.6-18.9). The best overall response rate was 60.0% (36.1-80.9), and the median progression-free survival was 11.6 months (2.9-20.3). The median progression-free survival in the p53 abnormal group (n = 9) was 3.4 months (3.0-3.8); however, progression-free survival did not reach the median (P < 0.001) in the mismatch repair-deficient/no specific molecular profile group (n = 11). Symptomatic immune-related adverse events (except hypothyroidism) occurred in 4/20 (25.0%) patients, and partial responses were observed in all cases. No treatment-related deaths occurred. CONCLUSION: The p53abn group in the Proactive Molecular Risk Classifier for Endometrial Cancer classification has a poor prognosis even after treatment with lenvatinib/pembrolizumab.

Comparison of treatment outcomes between first-line chemotherapy with or without bevacizumab for advanced ovarian, fallopian tube, and primary peritoneal cancer (Tohoku gynecologic cancer unit: TGCU-RS001 study).

BACKGROUND: Outcomes with and without bevacizumab as first-line chemotherapy in Japanese-only ovarian cancer patients have not been reported. In this study, we report a retrospective study conducted at the Tohoku Gynecologic Cancer Unit. PATIENTS AND METHODS: The study included 453 patients with stage III/IV ovarian, fallopian tube, and primary peritoneal cancer who received first-line platinum-based chemotherapy. The patients were divided into two groups: bevacizumab (168 patients) and without bevacizumab (285 patients). The primary endpoint was the rate of platinum-resistant recurrence and the secondary endpoints were the antitumor response, progression-free survival, overall survival, and adverse events. RESULTS: The objective response rates for patients with measurable diseases treated with and without bevacizumab were 84.5% and 73.0%, respectively (P = 0.0066). Platinum-resistant recurrence in the groups treated with and without bevacizumab was noted in 31 (18.4%) and 111 (38.6%) patients, respectively (P < 0.0001). The median progression-free survival for the bevacizumab and without bevacizumab groups was 23 and 15 months, respectively (P = 0.0002), and the median overall survival was not reached and 49 months, respectively (P = 0.0005). Hypertension of grade 3 or higher was observed in 21 patients (12.5%) in the bevacizumab group (P < 0.001), and proteinuria was observed in 18 patients (10.7%) and 1 patient (0.3%) in the bevacizumab and without bevacizumab groups, respectively (P < 0.001). Intestinal perforation was observed in only one patient (0.6%) in the bevacizumab group. CONCLUSION: Combination and maintenance with bevacizumab in primary chemotherapy for advanced ovarian, fallopian tube, and primary peritoneal cancer was effective in reducing platinum-resistant recurrence rates and prolonging progression-free and overall survival.

Expectations and Challenges of First-Line Maintenance Therapy for Advanced Ovarian Cancer.

The incidence of ovarian cancer, which has had a poor prognosis, is increasing annually. Currently, the prognosis is expected to improve with the use of molecular-targeted drugs and immune checkpoint inhibitors as maintenance therapies after the first-line chemotherapy. The GOG218 and ICON7 studies reported the usefulness of bevacizumab and the SOLO-1 and PRIMA (A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy) studies have reported the usefulness of olaparib and niraparib, respectively. The ATHENA study investigating the usefulness of rucaparib is currently ongoing. Although clinical studies of immune checkpoint inhibitors are lagging in the field of gynecology, many clinical studies using programmed death cell-1 (PD-1) and PD-1 ligand 1 (PD-L1) antibodies are currently ongoing. Some biomarkers have been identified for molecular-targeted drugs, but none have been identified for immune checkpoint inhibitors, which is a challenge that should be addressed in the future.

Comparison of Postoperative Adjuvant Chemotherapy and Concurrent Chemoradiotherapy for FIGO2018 Stage IIIC1 Cervical Cancer: A Retrospective Study.

Background and Objectives: In October 2018, the International Federation of Gynecology and Obstetrics (FIGO) revised its classification of advanced stages of cervical cancer. The main points of the classification are as follows: stage IIIC is newly established; pelvic lymph node metastasis is stage IIIC1; and para-aortic lymph node metastasis is stage IIIC2. Currently, in Japan, radical hysterectomy is performed in advanced stages IA2 to IIB of FIGO2014, and concurrent chemoradiotherapy (CCRT) is recommended for patients with positive lymph nodes. However, the efficacy of CCRT is not always satisfactory. The aim of this study was to compare postoperative adjuvant chemotherapy (CT) and postoperative CCRT in stage IIIC1 patients. Materials and Methods: Of the 40 patients who had undergone a radical hysterectomy at Iwate Medical University between January 2011 and December 2016 and were pathologically diagnosed as having positive pelvic lymph nodes, 21 patients in the adjuvant CT group and 19 patients in the postoperative CCRT group were compared. Results: The 5 year survival rates were 77.9% in the CT group and 74.7% in the CCRT group, with no significant difference. There was no significant difference in overall survival or progression-free survival between the two groups. There was no significant difference between CT and CCRT in postoperative adjuvant therapy in the new classification IIIC1 stage. Conclusions: The results of the prospective Japanese Gynecologic Oncology Group (JGOG) 1082 study are pending, but the present results suggest that CT may be a treatment option in rural areas where radiotherapy facilities are limited.

Phase II clinical study of neoadjuvant chemotherapy with CDDP/CPT-11 regimen in combination with radical hysterectomy for cervical cancer with a bulky mass.

BACKGROUND: We examined the efficacy and safety of neoadjuvant chemotherapy (NAC) with the CPT-11 + CDDP regimen in combination with radical hysterectomy. SUBJECTS AND METHODS: The subjects were 42 patients with stages IB2 to IIIB squamous cell carcinoma of the uterine cervix with a bulky mass. CDDP at 70 mg/m2 was intravenously administered on day 1 and CPT-11 at 70 mg/m2 was intravenously administered on days 1 and 8 of a 21-day cycle. In principle, two cycles were administered followed by radical hysterectomy. We examined antitumor efficacy, adverse events, completion rate of radical hysterectomy, operative time, surgical blood loss, progression-free survival (PFS), and overall survival (OS). RESULTS: The antitumor effect was complete response in 7 patients, partial response in 28, stable disease in 6, and progressive disease in 1; the response rate was 83.3 % (95 % confidence interval, 68.6-93.0). Grade 3 or more severe neutropenia, anemia, and platelet count decreases were noted in 23 (54.8 %), 4 (9.5 %), and 1 (2.4 %) patient, respectively. Grade 3 nausea occurred in 3 patients (7.1 %), vomiting in 1 (2.4 %), and grade 3 febrile neutropenia in 2 (7.1 %). The completion rate of radical hysterectomy was 88.1 %. The median operative time and surgical blood loss were 260 min (range, 210-334) and 500 ml (range, 393-898), respectively. The 5-year PFS rate was 67.2 %, and the 5-year OS rate was 68.0 %. In multivariate analysis, lymph node metastasis before NAC [hazard ratio (HR), 34.88] and non-response to NAC (HR 30.58) were significant prognostic factors. CONCLUSION: NAC with the CDDP/CPT-11 regimen achieves a high antitumor efficacy with moderate adverse reactions, allowing safe radical hysterectomy, and is thus considered to be a useful therapeutic method that can improve prognosis.

Analysis of prognostic factors for patients with bulky squamous cell carcinoma of the uterine cervix who underwent neoadjuvant chemotherapy followed by radical hysterectomy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is not yet widely recommended for the treatment of stage I/II cervical cancer. However, it may be possible to achieve a favorable outcome by selecting appropriate patients. In the present study, prognostic factors were retrospectively investigated to obtain data for devising individualized NAC. PATIENTS AND METHODS: The subjects were 33 patients with bulky stage Ib2-IIb squamous cell carcinoma (SCC) of the uterine cervix who gave consent and were scheduled to undergo radical hysterectomy. The patients intravenously received irinotecan 70 mg/m(2) on days 1 and 8 and cisplatin 70 mg/m(2) on day 1 of a 21-day course, and two courses were performed in principle. The potential prognostic factors investigated were age, performance status (PS), clinical stage, lymph node metastasis and tumor size before NAC, SCC antigen value, anti-tumor response, histological effect of NAC, lymph node metastasis in resected specimens, and postoperative adjuvant therapy after NAC. The impacts of these factors on overall survival (OS) were calculated with the Cox regression model. RESULTS: According to the univariate analysis, lymph node metastasis before NAC, SCC antigen value after NAC, anti-tumor response, and histological effect of NAC significantly influenced OS. These factors were tested in a multivariate model, and significant prognostic factors were lymph node metastasis before NAC (hazard ratio 0.116, P = 0.027) and anti-tumor response (hazard ratio 0.025, P = 0.003). CONCLUSION: The presence or absence of lymph node metastasis by computed tomography imaging was the only significant prognostic factor identified during the pre-NAC period.

Clinical significance of atypical glandular cells in the Bethesda system 2001: a comparison with the histopathological diagnosis of surgically resected specimens.

Forty-one patients diagnosed with atypical glangular cells (AGC) underwent surgery, and the histopathological diagnosis results for the resected specimens and the clinical features were analyzed. Out of 41 patients, final pathological diagnosis was endometrial cancer in 13 patients, cervical adenocarcinoma in 8, AIS in 7, CIN3 in 6, others in 2, and no lesions in 5. In comparison with previous reports, malignant or premalignant lesions were detected more frequently in patients with AGC who underwent surgery. We believe that conization or hysterectomy aimed at diagnosis and treatment, as well as endometrial histodiagnosis, should be carried out aggressively in patients with AGC.

Pilot study of intraperitoneal administration of triamcinolone acetonide for cancerous ascites in patients with end-stage gynecological cancer.

OBJECTIVE: Patients with end-stage cancer have poorly controlled ascites retention resulting due to cancerous peritonitis. We intraperitoneally administered triamcinolone acetonide (TA) to patients with end-stage gynecological cancer as a pilot study, and our treatment results are reported herein. PATIENTS AND METHODS: We enrolled 26 patients with end-stage gynecological cancer requiring frequent abdominal paracentesis for ascites drainage between April 2010 and September 2012. The volume of ascites drainage was 2000 to 3000 mL per drainage session, and TA at 10 mg/kg was intraperitoneally administered after drainage. We compared abdominal paracentesis intervals, performance status (PS), total protein level, albumin level, white blood cell count, changes in C-reactive protein (CRP) level, and adverse events before and after TA use. RESULTS: Triamcinolone acetonide was administered to 26 patients for a total of 59 times. The abdominal paracentesis intervals, PS, and mean (SD) of C-reactive protein before and after TA use were 13.2 (12.6) days and 21.9 (23.6) days (P = 0.0117), 2.4 (0.7) and 1.6 (1.1) (P < 0.0001), and 7.5 (5.2) mg/dL and 5.5 (5.0) mg/dL (P = 0.007), respectively. With regard to adverse events, abdominal pain of grade 2 was observed once (1.7%), but there were no other acute adverse events. Four subjects (15.4%) had intestinal perforation. CONCLUSIONS: Intraperitoneal administration of TA after drainage was considered to be a useful treatment, as it seems to extend paracentesis intervals and improve PS while maintaining quality of life for end-stage gynecological cancer patients with massive ascites.

A pilot study of oxaliplatin with oral S-1 as second-line chemotherapy for patients with recurrent adenocarcimona of the uterine cervix.

BACKGROUND: The efficacy and safety of S-1/oxaliplatin (SOX) therapy in patients with recurrent adenocarcinoma of the uterine cervix were examined in a pilot study. PATIENTS AND METHODS: S-1 was orally administered for 14 days at a dose of 80-120 mg/body/day to 7 patients with recurrent adenocarcinoma of the uterine cervix, with oxaliplatin being administered intravenously at a dose of 100 mg/m(2) on day 1. Each therapy cycle was 21 days, and the patients received 6 cycles at most. The antitumor effect, adverse events, progression-free survival (PFS), and overall survival (OS) were investigated. RESULTS: The median age of the patients was 49 years. The antitumor effect was rated as a complete response in 2 patients, partial response in 2, and stable disease in 3. The overall response rate was 57.1 %, and the disease control rate was 100 %. Regarding hematological toxicities of grade 3 or more, leukopenia, neutropenia and thrombocytopenia occurred in 42.9, 28.6 and 14.3 %, respectively; regarding non-hematological toxicities, grade 3 rectovaginal fistula occurred in 14.3 %, as well as grade 2 fatigue in 14.3 % of the patients. The median PFS and OS were 5 months (range 3-9 months) and 7 months (range 4-43 months), respectively. CONCLUSIONS: These results suggest that SOX therapy is useful for the treatment of recurrent adenocarcinoma of the uterine cervix, having a promising antitumor effect and minimal adverse effects. It was also suggested that SOX therapy may contribute to improving the prognosis for patients with adenocarcinoma of the uterine cervix.

Triple simultaneous primary invasive gynecological malignancies: a case report.

Double gynecologic cancer (primary cancers in two organs) is relatively rare. However, triple gynecologic cancer (primary cancers in three organs) is extremely rare. We experienced a case of triple cancer, with primary cervical, endometrial and ovarian cancers, each showing different histopathological features. A 50-year-old woman with a preoperative diagnosis of cervical cancer stage Ib1 with a pathological diagnosis of mucinous adenocarcinoma underwent radical hysterectomy. The pathological diagnoses of the extracted masses were endometrioid adenocarcinoma in the uterine corpus and serous adenocarcinoma in the left ovary. Consequently, triple cancer was diagnosed. After the operation, six cycles of a paclitaxel/carboplatin regimen were administered, and no relapse of the cancers has been observed to date. To our knowledge, this is only the second case report in the international literature of concurrent gynecologic triple cancers of epithelial origin; that is, invasive cervical, endometrial and ovarian cancers, each with different histopathological features.

Recurrent cervical cancer in a patient who was compound heterozygous for UGT1A1*6 and UGT1A1*28 presenting with serious adverse events during irinotecan hydrochloride/nedaplatin therapy.

There have been no case reports of the risk of serious adverse events associated with the administration of irinotecan hydrochloride (CPT-11) in patients with gynecologic cancer who are compound heterozygous for UGT1A1*6 and UGT1A1*28. A 71-year-old patient presented with recurrent stage IIIb cervical cancer. Combined chemotherapy was initiated with CPT-11 (60 mg/m² on days 1 and 8) plus nedaplatin (NDP; 80 mg/m² on day 1), with each cycle lasting for 28 days. The patient was a compound heterozygote for UGT1A1*6 and UGT1A1*28. Hematotoxic adverse events observed during the chemotherapy were grade 4 neutropenia, grade 3 anemia, and grade 4 thrombocytopenia, and the non-hematotoxic adverse events were grade 3 diarrhea and grade 3 fatigue. The findings in this patient indicate that CPT-11 should be administered with great care, even at a dose of 60 mg/m², in patients receiving combined therapy with CPT-11 and NDP who are compound heterozygous for UGT1A1*6 and UGT1A1*28.

Efficacy and Safety of Platinum-based Chemotherapy With Bevacizumab Followed by Bevacizumab Maintenance for Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer During PARP Inhibitor Therapy: A Multicenter Retrospective Study.

BACKGROUND/AIM: In recent years, the usefulness of poly ADP-ribose polymerase (PARP) inhibitors as subsequent maintenance therapy with poly ADP-ribose polymerase (PARP) inhibitors has been reported. However, it has been reported shown that platinum-based chemotherapy has a low response rate and short progression-free survival for recurrent platinum-sensitive ovarian cancer during treatment with PARP inhibitor therapy. This retrospective study evaluated platinum-based chemotherapy with bevacizumab (BEV) followed by BEV maintenance in these recurrent patients. PATIENTS AND METHODS: Efficacy and safety were evaluated in 23 patients with ovarian, fallopian tube, or primary peritoneal cancer diagnosed with platinum-sensitive recurrence during PARP inhibitor treatment (administered from April 2019 to December 2022). Platinum-based chemotherapy included either paclitaxel with carboplatin, paclitaxel with cisplatin, docetaxel with carboplatin, or doxorubicin with carboplatin. BEV was administered in combination with any of these chemotherapies agents. Chemotherapy was administered for 6 cycles and BEV was administered up to 21 cycles. RESULTS: The median numbers of cycles of platinum-based chemotherapy and BEV administration were 6 and 8, respectively. Complete response was observed in four patients (17.4%), partial response in 15 (65.2%), stable disease in two (8.7%), and progressive disease in two (8.7%). Objective response and disease control rates were 82.6% and 91.3%, respectively. Grade 3 or higher hematological toxicity occurred in 8 patients, with leukopenia, neutropenia in 14, anemia in 5, and thrombocytopenia in 4. On the other hand, non-hematological toxicities included hypertension in three patients, proteinuria in two, constipation in one, and carboplatin hypersensitivity in four. Only one patient discontinued chemotherapy due to an adverse event of proteinuria. No treatment-related deaths occurred. CONCLUSION: Platinum-based chemotherapy with BEV followed by BEV maintenance for platinum-sensitive recurrence during PARP inhibitor treatment was shown to be efficacious and safe. This combination should be further evaluated in larger randomized clinical trials.

A Phase II Study of S-1 plus Oxaliplatin for Patients with Recurrent Non-Squamous Cell Carcinoma of the Uterine Cervix (Tohoku Gynecologic Cancer Unit: TGCU206 Study).

Recurrent non-squamous cell carcinoma (non-SCC) of the uterine cervix is resistant to treatment and has a poor prognosis. The efficacy and safety of S-1/oxaliplatin (SOX) therapy in patients with recurrent non-SCC was examined in a phase II study. Fifteen patients were enrolled between August 2013 and March 2023. S-1 was administered orally at a daily dose of 80-120 mg for 14 days, and oxaliplatin was administered intravenously at a dose of 100 mg/m2 on day 1. Each treatment cycle lasted 21 days. The anti-tumor effects, adverse events, progression-free survival (PFS), and overall survival (OS) were investigated. The median patient age was 54 (41-74) years. The anti-tumor effect was rated as a partial response in five patients, stable disease in four, and progressive disease in 6. The overall response rate was 33% and the disease control rate was 60%. Regarding hematologic toxicities of grade 3 or more severity, leukopenia, neutropenia, anemia, and thrombocytopenia occurred in 26.6-40.0%. None of the patients discontinued the treatment because of adverse events. The median PFS and OS were 6 months (95% confidence interval [CI]: 2-11 months) and 22 months (95% CI: 11-23 months), respectively. No treatment-related deaths occurred. These results suggest that SOX therapy is useful for the treatment of recurrent non-SCC with promising anti-tumor effects and minimal adverse events.

Tako-Tsubo cardiomyopathy caused immediately following cesarean section delivery of triplets: a case report.

The name 'tako-tsubo' cardiomyopathy was initially used to describe a unique 'short-neck round-flask'-shaped form of left ventricular apical ballooning, resembling a Japanese tako-tsubo, a jar (tsubo) used for capturing octopus (tako). Tako-tsubo cardiomyopathy exhibits acute onset, transient left ventricular apical wall motion abnormalities with chest symptoms and minimal myocardial enzymatic release, mimicking acute myocardial infarction in patients without angiographic stenosis on coronary angiography. There have been few case reports on tako-tsubo cardiomyopathy, and this disorder is especially rare in pregnant women. A 30-year-old woman who was pregnant with triplets, and had been treated with ritodrine hydrochloride for 12 weeks for threatened premature delivery, underwent cesarean section with spinal anesthesia at 30 weeks' gestation. Three hours later, she complained of acute chest pain, dyspnea and episodes of unconsciousness. She was transferred to the intensive care unit and intubated for ventilatory support. We diagnosed heart failure due to tako-tsubo cardiomyopathy based on heart ultrasonography, blood tests, chest X-ray, electrocardiogram and myocardial scintigraphy. She was extubated from the ventilator after 3 days of catecholamine, furosemide and carperitide administration. She was discharged from the hospital on day 53 without symptoms.

Case of peptide-YY-producing strumal carcinoid of the ovary: a case report and review.

Ovarian carcinoid is a rare tumor accounting for approximately 0.1% of all ovarian malignancies. We describe a case of peptide-YY-producing strumal carcinoid of the ovary associated with severe constipation. A 48-year-old woman was found to have a pelvic mass on ultrasonography when she visited her primary doctor for a health check-up. She was thus referred to our department. Magnetic resonance imaging revealed a solid right ovarian tumor 60 × 50 mm in size. The patient underwent a right adnexectomy and was histopathologically diagnosed as having strumal carcinoid of the ovary. On immunohistochemical examination, the tumor cells were positive for peptide YY. The patient's constipation resolved rapidly after surgery. Based on her clinical course, her constipation was considered to have been caused by the strumal carcinoid of the ovary. The clinical course of this case supports the previously recognized correlation between peptide-YY-producing ovarian carcinoid and constipation.

Efficacy and Safety of Platinum Rechallenge in Patients With Platinum-resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer: A Multicenter Retrospective Study.

BACKGROUND/AIM: Ovarian cancer diagnosed with platinum-resistant recurrence has very poor prognosis and single-agent chemotherapy with no cross-resistance to prior chemotherapy is recommended for its treatment. In this study, we retrospectively evaluated the efficacy and safety of platinum rechallenge therapy for once diagnosed with platinum-resistant ovarian cancer who had a platinum-free interval (PFI) of at least 6 months. PATIENTS AND METHODS: The study included 49 patients who received platinum rechallenge therapy for ovarian, fallopian tube or primary peritoneal cancer who were once diagnosed with platinum-resistant recurrence between January 2010 and March 2021 and evaluated the efficacy and safety of this treatment. In addition, patient background factors were identified, and independent prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS: A complete response was noted in 7 cases, partial response in 21, stable disease in 9, and progressive disease in 10. The response and disease control rates were 55% and 76%, respectively. The median PFS and OS were 8.5 months and 35.8 months, respectively. The independent prognostic factor was PFI for OS, and there was no independent prognostic factor for PFS. Seven patients discontinued chemotherapy owing to serious adverse events, including one patient with treatment-related death. CONCLUSION: Platinum rechallenge therapy for patients with platinum-resistant recurrence did not cause previously unreported adverse events, and the adverse events were manageable. In addition, high response and disease control rates were observed, as well as long-term OS. Platinum rechallenge therapy for platinum-resistant ovarian cancer may be a viable treatment option.

Phase II clinical study of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of recurrent ovarian cancer (Tohoku Gynecologic Cancer Unit 101 Group Study).

OBJECTIVE: To evaluate the efficacy and safety of the combination chemotherapy regimen of irinotecan plus oral etoposide for the treatment of patients with recurrent ovarian cancer after previous treatment with platinum and taxane agents. PATIENTS AND METHODS: A total of 42 patients with recurrent ovarian cancer who had an evaluable lesion and provided informed consent for participation in the present study were analyzed. Irinotecan was administered intravenously at a dose of 60 mg/m on days 1 and 15. Etoposide was administered orally at a daily dose of 50 mg/body weight from days 1 to 21. A 28-day period comprised one cycle. The tumor response, adverse events, progression-free survival, and overall survival were examined. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors and the serum CA125 levels (Gynecologic Cancer Intergroup criteria). Adverse events were assessed according to the NCI-CTCAE (version 3.0). RESULTS: Partial response was observed in 21 patients, stable disease in 14 patients, and progressive disease in 7 patients. The response rate was 50.0%, and the clinical benefit (partial response + stable disease) rate was 83.3%. Hematological toxicities of at least grade 3 severity included leukopenia in 21 patients (50.0%), neutropenia in 22 patients (52.4%), thrombocytopenia in 1 patient (2.4%), anemia in 9 patients (21.4%), and febrile neutropenia in 3 patients (7.1%). Nonhematological toxicities of at least grade 3 severity included queasy feeling in 5 patients (11.9%), vomiting in 3 patients (7.1%), and diarrhea in 2 patients (4.8%). Acute myeloid leukemia occurred in one patient (2.4%). CONCLUSIONS: It is suggested that combination chemotherapy with irinotecan plus oral etoposide offers significant clinical benefit to patients with recurrent ovarian cancer previously treated with platinum and taxane agents.

Novel Therapeutic Strategies for Refractory Ovarian Cancers: Clear Cell and Mucinous Carcinomas.

Ovarian cancer has the worst prognosis among gynecological cancers. In particular, clear cell and mucinous carcinomas are less sensitive to chemotherapy. The establishment of new therapies is necessary to improve the treatment outcomes for these carcinomas. In previous clinical studies, chemotherapy with cytotoxic anticancer drugs has failed to demonstrate better treatment outcomes than paclitaxel + carboplatin therapy. In recent years, attention has been focused on treatment with molecular target drugs and immune checkpoint inhibitors that target newly identified biomarkers. The issues that need to be addressed include the most appropriate combination of therapies, identifying patients who may benefit from each therapy, and how results should be incorporated into the standard of care for ovarian clear cell and mucinous carcinomas. In this article, we have reviewed the most promising therapies for ovarian clear cell and mucinous carcinomas, which are regarded as intractable, with an emphasis on therapies currently being investigated in clinical studies.

Anti-Mϋllerian hormone and 3D-power Doppler histogram: markers of ovarian function with in vitro fertilization treatment.

PURPOSE: To investigate the ability of three-dimensional (3D) ultrasonography and anti-Mϋllerian hormone (AMH) to predict successful embryo development in patients undergoing in vitro fertilization (IVF) treatment. METHODS: We prospectively studied 28 patients undergoing IVF treatment, using 3D ultrasound Sono automatic volume calculation (AVC) and a 3D-power Doppler volume histogram. Sono AVC was used to automatically measure the number and volume of follicles. The volume histogram was used to measure the vascularization index (VI), flow index, and vascularization flow index in the ovaries. Serum AMH (S-AMH) was determined by enzyme immunoassay (ng/ml). RESULTS: The number of embryos isolated was 3.3 ± 2.8. The S-AMH of the patients who were under 35 years of age (0.570 ± 0.216 ng/ml) was higher than that in the patients over 40 years of age (0.377 ± 0.071 ng/ml; p = 0.0003). Principal component analyses determined that the quality of the embryo depended on the patients's age, S-AMH, and VI of the ovary. The receiver operating characteristic (ROC) curve showed that the cutoff for the S-AMH was 0.2855 ng/ml, and the optimal age of the patient was 32.5 years, when implanted with an embryo on day 16. CONCLUSIONS: We demonstrated that investigating the relationships between the number of the embryo and ovarian function, using a combination of AMH with a volume histogram, might be useful to predict the response to IVF treatment.

[Results of neoadjuvant chemotherapy using tri-weekly CDDP/CPT-11 for locally advanced cervical cancer].

OBJECTIVE: We assessed the antitumor response and safety of neoadjuvant chemotherapy (NAC) using cisplatin (CDDP) and irinotecan(CPT-11)given every three weeks for locally advanced cervical cancer with a bulky mass. SUBJECTS AND METHODS: Nineteen patients with cervical squamous cell cancer in FIGO stage of Ib2 to IIb were enrolled in this study. The FIGO stages were Ib2 in 5 patients, IIa in 2 patients, and IIb in 12 patients. One course of the chemotherapy regimen consisted of intravenous administrations of CDDP at a dose of 70 mg/m 2(day 1)and CPT-11 at 70 mg/m 2 (days 1 and 8) for 21 days, and two courses were administered. This chemotherapy was assessed for antitumor response, adverse events, complete surgical removal rate, progression-free survival time, and overall survival time. RECIST and NCI-CTCAE were used to determine antitumor response and adverse events, respectively. RESULTS: The results of assessment of the antitumor response showed CR in 3 patients(15. 8%), PR in 14(73. 7%), SD in 1 (5. 3%), and PD in 1(5. 3%). Neutropenia of grade 3 or higher occurred in 13 patients(68. 4%). Anemia occurred in 2 patients(10. 5%), and thrombocytopenia in 1 patient(5. 3%). Nausea and vomiting were observed in 2 patients(10. 5%). All patients underwent a chemotherapy regimen consisting of two courses, and the rate of complete surgical removal was 94. 7%. The median observation period was 27 months; the progression-free survival time was 18 months, and survival time was 27 months. CONCLUSION: Adverse drug reactions to NAC with the CDDP/CPT-11 combination administered every three weeks were controllable. The antitumor response rate for this chemotherapy was high. These assessment results indicate that NAC with a CDDP/CPT-11 combination was useful for local advanced cervical cancer.