Phase II study of gemcitabine, cisplatin, and bevacizumab for first recurrent and refractory ovarian clear cell carcinoma Kansai Clinical Oncology Group-G1601.

Patients with advanced ovarian clear cell carcinoma (CCC) have a poor prognosis in the absence of an effective standard treatment. Combination therapy with gemcitabine, cisplatin, and bevacizumab (GPBev) is promising for ovarian CCC. Thus, we conducted a multi-institutional, phase II trial in Japan to examine the efficacy and safety of GPBev for CCC. This is the first study on the use of GPBev for CCC. Eighteen patients (median age, 56.5 years) with pathologically confirmed first recurrent or refractory CCC and having evaluable regions, as assessed using RECIST, were recruited between January 2017 and May 2019. Gemcitabine (1000 mg/m 2 ), cisplatin (40 mg/m 2 ), and bevacizumab (10 mg/kg) were administered intravenously on days 1 and 15, every 28 days, for 6-10 cycles, until disease progression or intolerable toxicity. The primary endpoint was overall response rate (ORR). The secondary endpoints included disease control rate (DCR) and adverse events (AEs). Fifteen patients (83.3%) completed 6-10 cycles of treatment; three patients (two with AEs and one with progressive disease) did not. The ORR was 61.1% [complete response (CR) 3 and partial response (PR) 8] and DCR was 88.9% (CR 3, PR 8, and stable disease 5). Grade 3 and 4 hematological AEs were observed in 16.7 and 5.6% of the patients, respectively. Nonhematological AEs of grades 3 and 4 were observed in 27.8 and 5.6% of the patients, respectively. GPBev is a promising therapy for CCC owing to the high ORR and acceptable toxicity for the first recurrence and refractory CCC.

Veliparib with frontline chemotherapy and as maintenance in Japanese women with ovarian cancer: a subanalysis of efficacy, safety, and antiemetic use in the phase 3 VELIA trial.

BACKGROUND: The phase 3 VELIA trial evaluated veliparib with carboplatin/paclitaxel and as maintenance in patients with high-grade serous ovarian carcinoma. METHODS: Patients with previously untreated stage III-IV high-grade serous ovarian carcinoma were randomized 1:1:1 to control (placebo with carboplatin/paclitaxel and placebo maintenance), veliparib-combination-only (veliparib with carboplatin/paclitaxel and placebo maintenance), or veliparib-throughout (veliparib with carboplatin/paclitaxel and veliparib maintenance). Randomization stratification factors included geographic region (Japan versus North America or rest of the world). Primary end point was investigator-assessed median progression-free survival. Efficacy, safety, and pharmacokinetics were evaluated in a subgroup of Japanese patients. RESULTS: Seventy-eight Japanese patients were randomized to control (n = 23), veliparib-combination-only (n = 30), and veliparib-throughout (n = 25) arms. In the Japanese subgroup, median progression-free survival for veliparib-throughout versus control was 27.4 and 19.1 months (hazard ratio, 0.46; 95% confidence interval, 0.18-1.16; p = 0.1 [not significant]). In the veliparib-throughout arm, grade 3/4 leukopenia, neutropenia, and thrombocytopenia rates were higher for Japanese (32%/88%/32%) versus non-Japanese (17%/56%/28%) patients. Grade 3/4 anemia rates were higher in non-Japanese (65%) versus Japanese (48%) patients. Early introduction of olanzapine during veliparib monotherapy maintenance phase may help prevent premature discontinuation of veliparib, via its potent antiemetic efficacy. CONCLUSIONS: Median progression-free survival was numerically longer in Japanese patients in the veliparib-throughout versus control arm, consistent with results in the overall study population. Pharmacokinetics were comparable between Japanese and non-Japanese patients. Data for the subgroup of Japanese patients were not powered to show statistical significance but to guide further investigation.

Adjuvant Chemotherapy for Endometrial Cancer (ACE) trial: A randomized phase II study for advanced endometrial carcinoma.

This study evaluated the feasibility and efficacy of three postoperative adjuvant chemotherapy regimens for endometrial cancer. Endometrioid cancer patients with intermediate-risk stage I and II or high-risk stage III and IV disease were randomly assigned to receive six cycles of either paclitaxel-epirubicin-carboplatin (TEC), paclitaxel-anthracycline (doxorubicin)-carboplatin (TAC), or dose-dense paclitaxel-carboplatin (ddTC). The primary end-point was the completion rate (CRate) of six cycles of treatment. The secondary end-points were progression-free survival (PFS) and overall survival (OS). One hundred and one patients were treated as follows: 33 received TEC, 33 TAC, and 35 ddTC. The CRates for TEC, TAC, and ddTC were 94%, 64%, and 69%, respectively (P = .005). The TEC CRate was significantly higher than for the other two groups. However, the PFS and OS outcomes were not statistically different between the three groups. The 2-year survival rates were 94%, 97%, and 97% for TEC, TAC, and ddTC, respectively. When compared to the current standard treatments for endometrial cancer, TEC is a promising candidate for a phase III trial based on its significantly superior CRate and equivalent PFS and OS. This study is registered with UMIN Clinical Trials Registry (UMIN000008911).

[Metastatic Tumor of the Uterine Cervical Cancer Occurred in the Infratemporal Fossa].

A 46-year-old woman presented with discomfort in her right lateral gaze, right-sided headache, and facial numbness 17 days after concurrent chemoradiotherapy(CCRT)for a Stage ⅢB cervical cancer. The initial imaging investigations, maxillofacial and otolaryngology reviews did not reveal a diagnosis. After 54 days of CCRT, her symptoms deteriorated. Magnetic resonance imaging(MRI)showed a tumor in the right infratemporal fossa and its biopsy confirmed a metastatic cervical cancer. In view of the rapid deterioration and the potential visual loss, palliative intensity-modulated radiotherapy(IMRT) was given. Although the symptoms improved temporarily, multiple metastases were subsequently found. Despite chemotherapy, the patient died 11 months after developing the symptoms of infratemporal fossa metastasis.

Correlation of World Health Organization 2010 Classification for Gastroenteropancreatic Neuroendocrine Neoplasms with the Prognosis of Ovarian Neuroendocrine Neoplasms: Kansai Clinical Oncology Group-Protocol Review Committee/Intergroup Study.

BACKGROUND: In 2014, the World Health Organization (WHO) released a classification system introducing neuroendocrine neoplasms (NENs) of the female reproductive tract, excluding the ovaries. This study aimed to evaluate whether retrospective adaption of the gastroenteropancreatic (GEP)-NEN classification is feasible for ovarian NENs (O-NENs) and correlates with prognosis. METHODS: Sixty-eight patients diagnosed with carcinoid, small cell carcinoma (pulmonary type), paraganglioma, non-small/large cell neuroendocrine carcinoma (NEC), mixed NEC, or undifferentiated carcinomas at 20 institutions in Japan were included in this retrospective cross-sectional study. We identified O-NENs through central pathological review using a common slide set, followed by reclassification according to WHO 2010 guidelines for GEP-NENs. A proportional hazards model was used to assess the association of prognostic factors (age, stage, performance status, histology, and residual disease) with overall survival (OS) and progression-free survival (PFS). RESULTS: Of the 68 enrolled patients, 48 were eligible for analysis. All carcinoids (n = 32) were reclassified as NET G1/G2, whereas 14 of 16 carcinomas were reclassified as NEC/mixed adeno-NEC (MANEC) (Fisher's exact test; p < 0.01). The OS/PFS was 49.0/42.5 months and 6.5/3.9 months for NET G1/G2 and NEC/MANEC, respectively. Histology revealed that NEC/MANEC was associated with increased risk of death (HR = 48.0; 95% CI, 3.93-586; p < 0.01) and disease progression (HR = 51.6; 95% CI, 5.54-480; p < 0.01). CONCLUSION: Retrospective adaption of GEP-NEN classification to O-NENs is feasible and correlates well with the prognosis of O-NENs. This classification could be introduced for ovarian tumors.

[Clinical Application of Gemcitabine plus Cisplatin plus Bevacizumab Combination Chemotherapy for Ovarian Clear Cell Carcinoma].

Ovarian clear cell carcinoma(OCCC)shows a poor response to standard chemotherapy, and it is often difficult to choose a regimen for patients with recurrent OCCC. Several reports have suggested a synergistic effect between gemcitabine and cisplatin; another report suggested that gemcitabine, platinum, and bevacizumab are efficacious against recurrent ovarian cancer. We treated patients with OCCC using a combination chemotherapy regimen consisting of gemcitabine(1,000 mg/ m2)and cisplatin(40 mg/m2)on days 1 and 15, and bevacizumab(15 mg/kg)on day 1, with the cycle repeated every 4 weeks. Six patients received this therapy after informed consent, and 2 evaluable patients showed a partial response. Adverse events were mild, with Grade 3 anemia, leukopenia, and neutropenia occurring in 67%, 33%, and 17% of cases, respectively. No Grade 4 events were observed, including hematological or non-hematological toxicities. This suggests that a regimen of combined gemcitabine, platinum, and bevacizumab can be efficacious and feasible for the treatment of OCCC.

[Efficacy of Olaparib Treatment for Platinum-Sensitive Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancers].

We reviewed our clinical experience of olaparib treatment for patients with platinum-sensitive recurrent ovarian, fallopian tube, and peritoneal cancer. Of the 10 cases, the primary sites of cancer were the ovaries, fallopian tubes, and peritoneum in 7, 1 and 2 cases, respectively. The median period of treatment administration was 10 months. The observed Grade 3 or 4 adverse events as per the Common Terminology Criteria for Adverse Events version 4.0 were: anemia, leukopenia and neut r openia in 4, 4 and 3 cases, respectively. Eight cases needed treatment to be interrupted, and 5 cases required a reduction in dose. Three patients were treated for more than 12 months, while the others had to discontinue due to disease progression. However, none of the patients had to discontinue treatment due to adverse events. Therefore, it appears that olaparib can be safely used despite some patients requiring a withdrawal or reduction in treatment.

Phase 1/2 study of concurrent chemoradiotherapy with weekly irinotecan hydrochloride for advanced/recurrence uterine cancer: A multi-institutional study of Kansai Clinical Oncology Group.

OBJECTIVE: Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix, but it had not been effective for adenocarcinoma. Concurrent chemoradiotherapy using irinotecan hydrochloride (CPT-11) had been effective for colorectal cancer, thus, we chose CPT-11 as a candidate for gynecologic adenocarcinoma. To evaluate the maximum tolerated dose (MTD) of weekly CPT-11 with external pelvic radiotherapy, a phase 1/2 study was conducted according to modified Fibonacci method. METHODS: Eligible patients were advanced uterine cancer with measurable diseases [performance score (PS): 0-2]. Study period was from August 1st, 2002 to December 31st, 2008. The starting dose level (DL) of CPT-11 was 30 mg/m2 (DL1) given weekly for 4 weeks. Subsequently, dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m2 (DL4). The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d, once a day in weekday for five weeks and it amounted to 45 Gy (25 fractions) in total. RESULTS: Seventeen patients were enrolled. As for toxicities, one (1/17: 5.9%) grade (G) 4 neutropenia lasting 7 days had been seen in DL4. G2 diarrhea was identified in 35.3% (6/17) of the patients, and 11.8% (2/17) G3 diarrhea was observed in DL3 and DL4. Thus, the MTD of CPT-11 was defined as dose of 60 mg/m2. The recommended dose was decided as 50 mg/m2. The response rate was 88.2% [9 complete response (CR), 3 partial response (PR), 3 stable disease (SD), 2 not evaluable (NE)]. Disease control rate at 1 month after treatment completion was 100% but distant metastases were found in 24% (4/17) in longer outcome. CONCLUSIONS: MTD was 60 mg/m2 and recommended dose was set as 50 mg/m2. This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m2, and it might be effective even in adenocarcinoma of the uterus.

A phase II randomized controlled study of pegylated liposomal doxorubicin and carboplatin vs. gemcitabine and carboplatin for platinum-sensitive recurrent ovarian cancer (GOTIC003/intergroup study).

PURPOSE: To compare the efficacy, safety, and tolerability profiles of pegylated liposomal doxorubicin and carboplatin (PLDC) with those of gemcitabine and carboplatin (GC) for the treatment of patients with platinum-sensitive recurrent ovarian cancer. METHODS: Ovarian cancer patients with recurrence > 6 months after first-line platinum and taxane-based therapies were randomly assigned to PLDC [pegylated liposomal doxorubicin 30 mg/m2 plus carboplatin area under the curve (AUC) 5 mg/mL/min on day 1] every 4 weeks or GC (gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin AUC 4 mg/mL/min on day 1) every 3 weeks for at least 6 cycles. The primary endpoint was progression-free survival, and overall response rate, overall survival, toxicity, and dose administration were secondary endpoints. RESULTS: One-hundred patients (49 PLDC; 51 GC) were randomly assigned. Over a median follow-up of 24 months, the median progression-free survival was 12.0 months (95% CI 9.2-15.0) for PLDC and 9.8 months (8.9-12.3) for GC [HR 0.69 (0.455-1.047)] with a difference of 2.2 months. The response rate was 57.1% (41.0-72.3) for PLDC and 56.4% (39.6-72.2) for GC. No obvious differences in toxicity (G3/4) were noted between arms. The median relative dose intensity of planned dose per week was 88.9% for pegylated liposomal doxorubicin and 53.1% for gemcitabine (p < 0.0001). CONCLUSIONS: PLDC and GC are both good treatment candidates for platinum-sensitive recurrent ovarian cancer patients; however, the dose intensity was lower for GC than for PLDC. PLDC had a more favorable risk-benefit profile than that of GC for patients.

Multi-institutional phase II study of neoadjuvant irinotecan and nedaplatin followed by radical hysterectomy and the adjuvant chemotherapy for locally advanced, bulky uterine cervical cancer: A Kansai Clinical Oncology Group study (KCOG-G1201).

AIM: A multi-institutional phase II trial was conducted to determine the efficacy and toxicity of neoadjuvant chemotherapy with irinotecan and nedaplatin followed by radical hysterectomy and adjuvant chemotherapy for locally advanced, bulky stage IB2-IIB cervical cancer. METHODS: Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB2-II, bulky type (>4 cm in diameter) squamous cell carcinoma of the uterine cervix were enrolled. Irinotecan (60 mg/m2 ) was administered intravenously on days 1 and 8 and nedaplatin (80 mg/m2 ) was also administered on day 1 of every 21-day cycle. After two cycles of chemotherapy, a radical hysterectomy was performed. Until 6 weeks after the surgery, three to five cycles of the regimen were added as adjuvant chemotherapy. The primary endpoint was the 2-year relapse-free survival rate. The response rates and toxicities were evaluated as secondary endpoints. RESULTS: Thirty-two patients from seven institutions were enrolled in this study. The median age was 48 years (range 25-75 years). The average follow-up period was 37.8 months (15-71 months). Twenty-three patients completed the regimen as planned. The objective response rate (complete response + partial response) for the neoadjuvant chemotherapy regimen was 81.2%. The 2-year and 5-year relapse-free-survival rates were 87.5% and 78.8%, respectively. The incidence of grade 3/4 neutropenia was 6.3% and 34.4% during neoadjuvant and adjuvant treatment, respectively. All other toxicities were well tolerated. CONCLUSION: Our treatment showed efficacy and tolerability for patients with locally advanced, bulky stage IB2-IIB cervical cancer. This suggests that treatment has the potential to improve the prognosis compared to concurrent chemo-radiotherapy.

Phase II study of adjuvant chemotherapy with paclitaxel and nedaplatin for uterine cervical cancer with lymph node metastasis.

The purpose of this phase II trial was to assess the efficacy and toxicity of paclitaxel and nedaplatin (TN) as the initial postoperative adjuvant chemotherapy for uterine cervical cancer with lymph node metastases (LNM). Patients with FIGO stage IB1-IIA2 squamous cell carcinoma of the uterine cervix were enrolled. Histological confirmation of LNM was mandatory. Intravenous paclitaxel at 175 mg/m2 and nedaplatin at 80 mg/m2 were administered every 28-day cycle, of which there were 5 cycles after radical hysterectomy. Sixty-two patients were enrolled in the study from November 2011 to July 2015. Their median age was 48.5 years (range 28-64). The median tumor diameter was 37 mm (5-64). Overall, 30 patients (48.4%) had 1 metastatic lymph node, 11 (17.7%) had 2, 3 (4.8%) had 3, 5 (8.1%) had 4, and 13 (21.0%) had 5 or more. With a median follow-up of 45.7 months (range 23.4-69.5), the 2-year relapse-free survival and 2-year overall survival rates were 79.0% (90% CI, 69.0%-86.2%) and 93.5% (95% CI, 83.7%-97.5%), respectively. Almost all adverse events were relatively mild. Grade 3-4 adverse events (NCI-CTC ver. 4.0) that occurred in 5% or more of patients were neutropenia (60.7%) and infection (6.6%). The proportion of patients who completed 5 cycles of treatment was 90.3%. Postoperative adjuvant chemotherapy with TN for cervical cancer with LNM was demonstrated to be an effective and feasible treatment. A phase III trial is warranted to compare this with concurrent chemoradiotherapy.

Dendrite-Free Epitaxial Growth of Lithium Metal during Charging in Li-O2 Batteries.

Lithium (Li) dendrite formation is one of the major hurdles limiting the development of Li-metal batteries, including Li-O2 batteries. Herein, we report the first observation of the dendrite-free epitaxial growth of a Li metal up to 10-µm thick during charging (plating) in the LiBr-LiNO3 dual anion electrolyte under O2 atmosphere. This phenomenon is due to the formation of an ultrathin and homogeneous Li2 O-rich solid-electrolyte interphase (SEI) layer in the preceding discharge (stripping) process, where the corrosive nature of Br- seems to give rise to remove the original incompact passivation layer and NO3- oxidizes (passivates) the freshly formed Li surface to prevent further reactions with the electrolyte. Such reactions keep the SEI thin (<100 nm) and facilitates the electropolishing effect and gets ready for the epitaxial electroplating of Li in the following charge process.

Current status of tertiary debulking surgery and prognosis after secondary debulking surgery for recurrent Müllerian epithelial cancer in Japan: a retrospective analysis of 164 patients (KCOG-G1402).

BACKGROUND: This study aimed to evaluate the current status of secondary debulking surgery (SDS) and tertiary debulking surgery (TDS; performed for recurrence after SDS) and to assess the overall survival after recurrence of Müllerian epithelial cancer in Japan. We also evaluated the data of patients who underwent a fourth debulking surgery (i.e., quaternary debulking surgery (QDS)). METHODS: We conducted a retrospective study of 164 patients with recurrent Müllerian epithelial cancers (i.e., ovarian, tubal, and peritoneal cancers). The SDS was performed between January 2000 and September 2014 in 20 Japanese hospitals. Clinicopathological data were collected and analyzed. RESULTS: Of the 164 patients, 66 patients did not have a recurrence or died after SDS. Ninety-eight patients had a recurrence after SDS. Forty-three of the 98 patients underwent TDS; 55 of the 98 patients did not undergo TDS and were classified into the non-TDS group. The overall survival (OS) after SDS was significantly better in the TDS group than in the non-TDS group. The median OS after SDS was 123 and 42 months in the TDS group and non-TDS group, respectively. Of the 43 patients who received TDS, 11 patients were further treated with QDS. The median OS after SDS was 123 months for patients who underwent QDS. CONCLUSIONS: This multicenter study on the prognosis of post-SDS is apparently the first report on QDS in Japan. Patients undergoing TDS have a good prognosis, compared to patients in the non-TDS group. Novel drugs are being evaluated; however, debulking surgery remains a necessary treatment for recurrence.

[Comparison between Primary Debulking Surgery and Neo-Adjuvant Chemotherapy Followed by Interval Debulking Surgery for Patients with Stage III-IV Ovarian Cancer].

The current standard treatment for advanced ovarian cancer is primary debulking surgery(PDS). We may expect a good prognosis if complete debulking(no visible residual tumor)is possible. However, if complete surgery is not possible owing to the location of the tumor or poor performance status, neo-adjuvant chemotherapy(NAC)could be an alternative option. Interval debulking surgery(IDS)can be planned after NAC to try and achieve complete debulking surgery. We reviewed stage III and IV epithelial ovarian cancers treated at Kansai Rosai Hospital between January 2012 and January 2016. Fifty-one cases (PDS: 22 cases, NAC-IDS: 29 cases)were enrolled in our analysis. Progression-free survival(PFS), overall survival(OS), the successful complete surgery rate, and the contents and complications of the surgery were compared between the PDS and NAC-IDS groups. There was no significant difference in PFS and OS between the 2 groups(PFS: p=0.467, OS: p=0.685). Blood loss was larger in the PDS group(p=0.013). Patients in the NAC-IDS group were likely to be able to eventually achieve complete surgery(p=0.016). NAC followed by IDS is one of the effective treatment options for advanced ovarian cancers.

[A Retrospective Analysis of Systematic Lymphadenectomy for Loco-Regional(pT1)Epithelial Ovarian Cancer].

BACKGROUND: The incidence of lymph node metastasis in pT1 epithelial ovarian cancer is between 5% and 21%. Most cases with lymph node metastasis are those of serous carcinoma; it is relatively rare in mucinous carcinoma. Therefore, there is a recent trend to omit systematic lymphadenectomy in early stage mucinous carcinoma. The purpose of this study was to verify whether the omission of systematic lymphadenectomy in mucinous carcinoma is oncologically safe. METHODS: We reviewed all pT1 epithelial ovarian cancer cases that were treated in our hospital between January 2002 and December 2015. RESULTS: Fiftynine cases of pT1 epithelial ovarian cancer were included. The overall rate of lymph node metastasis was 6.8%(4 in 59). It was 6.5%(2 in 31)in clear cell carcinoma and 22.2%(2 in 9)in mucinous carcinoma. CONCLUSION: According to our study, lymph node metastasis in pT1 mucinous carcinoma has a rate of 22.2% and some affected cases were not detected by presurgery imaging studies. Therefore, we need to be careful about the omission of systematic lymphadenectomy in mucinous carcinoma.

[A Case Report of Post-Radiochemotherapy Perineum Abscess Concurrent with Recurrence of Vaginal Cancer for Which Total Pelvic Exenteration Was Performed].

We report a case of a woman who was suffering from post-radiochemotherapy perineum abscess concurrent with the recurrence of vaginal cancer for which total pelvic exenteration was performed. A 66-year-oldwoman presentedat our hospital with irregular genital bleeding in November 2014. A series of examinations showedthat she was suffering from vaginal cancer(cT2N0M0, cStage II ). A radiochemotherapy regimen(external irradiation 45 Gy/25 Fr, CDDP 40mg/m2, 5 course)was commencedin January 2015. In the meantime, MRI revealedsome therapeutic effect, but in October 2015, MRI indicated the enlargement of the primary tumor(PD). The chemotherapy regimen was alteredanda regimen of paclitaxel plus nedaplatin was commenced in November 2015 andw as continueduntil April 2016. MRI was performedin March 2016 to distinguish the therapeutic response between PR and CR. In May 2016, the patient complainedof an increasedfrequency of melena. Colonoscopy was performedto reveal Grade 3 radiation enteritis, andargon plasma coagulation was requiredto stop bleeding. In June 2016, MRI was performedandrevealedCR. In July 2016, however, the radiation enteritis led to rectovaginal fistula, for which we performed transverse colostomy. Thereafter, the necrotic tissue gradually expanded into the perineum area to involve the urethra. Recurrence of the cancer was suspected; therefore, we decided to perform total pelvic exenteration in December 2016. Pathological examination of the surgical specimen indicated the recurrence of the vaginal cancer. We report this rare case andd iscuss the usefulness of total pelvic exenteration for the recurrence of vaginal cancer.

A phase II study of postoperative concurrent carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy followed by consolidation chemotherapy in surgically treated cervical cancer patients with positive pelvic lymph nodes.

OBJECTIVES: A phase II study was conducted to evaluate the efficacy and toxicity of carboplatin plus paclitaxel (TC)-based postoperative concurrent chemoradiotherapy (CCRT) followed by TC-based consolidation chemotherapy in surgically-treated early-stage cervical cancer patients. METHODS: Women with surgically-treated early-stage cervical cancer with positive pelvic lymph nodes were eligible for this study. The patients were postoperatively treated with pelvic intensity modulated radiotherapy (50.4Gy) and concurrent weekly carboplatin (AUC: 2) and paclitaxel (35mg/m(2)) (TC-based CCRT). Three cycles of consolidation chemotherapy involving carboplatin (AUC: 5) and paclitaxel (175mg/m(2)) were administered after TC-based CCRT. RESULTS: Thirty-one patients were enrolled and treated. Overall, the treatment was well tolerated, and 26 patients (83.9%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up period of 36.5months, 2 patients (6.5%) had developed recurrent disease. The patients' estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 93.8%, respectively. In comparisons with historical control groups, TC-based CCRT followed by TC-based consolidation chemotherapy was found to be significantly superior to CCRT involving a single platinum agent in terms of PFS (p=0.026) and significantly superior to extended-field radiotherapy in terms of both PFS (p=0.0004) and OS (p=0.034). CONCLUSIONS: In women with surgically treated early-stage cervical cancer, pelvic TC-based CCRT followed by TC-based consolidation chemotherapy is feasible and highly effective. Future randomized trials are needed to verify the efficacy of this regimen.

Optimal cytoreductive surgery in patients with advanced uterine carcinosarcoma: A multi-institutional retrospective study from the Japanese gynecologic oncology group.

BACKGROUND: The benefits of cytoreductive surgery for uterine carcinosarcoma (UCS) are unknown. The objective of this study was to determine the impact of optimal surgery on advanced UCS patient survival. METHODS: We performed a multi-institutional, retrospective study of women diagnosed with stage IIIIV UCS between 2007 and 2012. Data were obtained retrospectively from medical records, including demographic, clinicopathologic, treatment, and outcome information. Optimal cytoreductive surgery was defined as surgery resulting in a maximum residual tumor of ≤1cm. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS), and the Cox regression model was used to examine the impact of selected factors on survival. RESULTS: A total of 225 UCS patients (median age, 63years) were identified, including 136 (60%) with stage III and 89 (40%) with stage IV disease. Among these patients, 170 (76%) received optimal cytoreductive surgery. The median follow-up time was 19months. The median PFS was 11.5months (95% confidence interval [CI], 10.6-13.4) and 8.1months (95% CI, 5.1-9.5) for patients who received optimal and suboptimal cytoreductive surgery, respectively (P<0.0001). The median OS was 37.9months (95% CI, 28.3-not reached) and 18months (95% CI, 9.6-21) for patients who received optimal and suboptimal cytoreductive surgery, respectively (P<0.0001). Residual tumor >1cm was associated with worse OS while pelvic lymph node dissection was associated with improved OS. CONCLUSION: Optimal cytoreductive surgery and pelvic lymph node dissection are associated with improved OS in advanced UCS patients.

Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy in gynecological cancer: KCOG-G1301 phase II trial.

PURPOSE: Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC. METHODS: This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy. RESULTS: Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events. CONCLUSIONS: Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.

Prognostic factors in patients with uterine carcinosarcoma: a multi-institutional retrospective study from the Japanese Gynecologic Oncology Group.

BACKGROUND: Uterine carcinosarcomas (UCSs) are rare and aggressive tumors. The prognostic factors are not sufficiently known. METHODS: We performed a multi-institutional, retrospective study of women with stage I-IV UCS, diagnosed between 2007 and 2012. Data obtained from medical records included demographic, clinicopathological, treatment, and outcome information. RESULTS: A total of 486 patients (median age 65 years) were identified-224 (46 %) were stage I, 32 (7 %) were stage II, 139 (28 %) were stage III, and 91 (19 %) were stage IV. Among them, 277 (57 %) had disease recurrence. Median disease-free survival (DFS) was 16.4 months [95 % confidence interval (CI) 15.7-27.2], and median overall survival (OS) was 72.0 months (95 % CI 43.0-not reached). In total, 454 (94 %) patients received adjuvant treatment, and 440 (91 %) received adjuvant chemotherapy. In multivariate analysis, stage III-IV disease, CA-125 level, and lymphovascular space invasion (LVSI) were significantly associated with shorter median DFS. Stage III-IV disease, performance status 2-4, ≥50 % myometrial invasion depth, and postsurgical residual tumor size >1 cm were significantly associated with shorter median OS. Conversely, pelvic lymph node lymphadenectomy was associated with improved DFS and OS. CONCLUSIONS: Stage, performance status, CA-125 level, LVSI, and myometrial invasion were associated with poor prognoses. Pelvic lymphadenectomy was associated with improved survival, and may be necessary for the surgical management of UCS.