Chemotherapy for advanced or recurrent cervical cancer

AbstractThe primary treatment options for cervical cancer are surgery and radiation for more than a century. However, over the last 40 years chemotherapy has been building up its reputation in the management of cervical cancer in various forms such as chemoradiation, neoadjuvant chemotherapy, and palliative chemotherapy for advanced or recurrent disease. Among these, in this review, chemotherapy for advanced or recurrent cervical cancer will be discussed

A case of minimal uterine serous carcinoma with distant lymph node metastasis without peritoneal dissemination

A 61-year old woman underwent total abdominal hysterectomy and pelvic lymph node dissection under the diagnosis of endometrial cancer. Although pelvic lymph nodes were positive for adenocarcinoma with psamomma bodies, no other lesion that was a primary lesion was verified. A postoperative study revealed the existence of para-aortic lymph node and supraclavicular lymph node metastases. Therefore, the endometrial biopsy specimen was reviewed. With the findings of p53 positivity by immunohistochemistry in the papillary part, the final histopathological diagnosis was changed to endometrial serous adenocarcinoma. Postoperative chemotherapy followed by radiotherapy for supraclavicular lymph node metastasis achieved complete response. This type of tumor must be considered in a differential diagnosis when metastatic papillary serous carcinoma is detected, but the primary site remains unknown

A randomized, double-blind, placebo-controlled, phase II study to assess the efficacy/safety of farletuzumab in combination with carboplatin plus paclitaxel or carboplatin plus pegylated liposomal doxorubicin (PLD) in women with low CA-125 platinum-sensitive ovarian cancer

Objectives: The primary objective of this study (MORAb-003-011/ENGOT-ov27) was to determine if farletuzumab (FAR) had superior efficacy compared with placebo (PLB) in improving progression-free survival (PFS) when added to carboplatin (carbo)/paclitaxel (pacli) or carbo/PLD, in subjects with platinum-sensitive ovarian cancer in first relapse (platinum-free interval: 6-36 months) with low cancer antigen 125 (CA-125). CA-125 inhibits target cell killing via antibody-dependent cellular cytotoxicity, thereby reducing the efficacy of immunotherapeutic antibodies. Subgroup analysis in a prior randomized Phase III study±FAR suggested that subjects with CA-125 levels ≤3 x upper limit of normal (ULN), showed superior PFS (hazard risk [HR] = 0.49) and overall survival (OS, HR = 0.44) compared with PLB. Methods: Eligibility included age ≥18 years old, CA-125 ≤3 x ULN (105 U/mL), high-grade serous epithelial ovarian cancer, and previous treatment with debulking surgery and first-line platinum-based chemotherapy. Subjects received 6 cycles with either carbo/pacli every 3 weeks or carbo/PLD in combination with either FAR [5 mg/kg weekly] or PLB in a 2:1 ratio. Maintenance treatment with FAR (5 mg/kg weekly) or PLB was given until disease progression. Tumor assessments were every 6 weeks during the Combination Treatment Phase and every 9 weeks during the Maintenance Treatment Phase. The study was designed to detect a PFS HR of 0.667 (33.3% risk reduction) with FAR compared with PLB with approximately 85% power and a 1-sided type I error rate of 0.10. The comparison of PFS between treatment groups was based on the log-rank test. The HR was estimated based on Cox\u27s proportional-hazards model. Results: A total of 214 subjects were randomized and enrolled, 142 with FAR+chemotherapy (FAR-CT) and 72 with placebo+chemotherapy (PLB-CT). The median PFS in the Intent-to-Treat [ITT] Population was not significantly different between treatment groups; 11.7 months (95% confidence interval [CI]: 10.2, 13.6) versus 10.8 months (95% CI: 9.5, 13.2) for FAR-CT and PLB-CT, respectively (HR = 0.89; 80% CI: 0.71, 1.11). An interim analysis of OS showed no significant difference between treatment groups. The overall response rate (ORR) was 69.6% in 96 subjects treated with FAR-CT versus 73.5% in 50 subjects treated with PLB-CT (p=0.53). No significant differences between treatment groups were observed for any other efficacy parameters. The safety profile of the 2 treatment groups was similar except for an increase in interstitial lung disease among the FAR cohort. Interstitial lung disease occurred in 7 of 141 (5.0%) subjects treated with FAR-CT (1 with Grade 1, 4 with Grade 2, and 2 with Grade 3) and none in subjects treated with PLB-CT. Conclusions: The combination of FAR-CT did not show signals of superior efficacy compared with PLB-CT in improving PFS or other efficacy parameters in subjects with platinum-sensitive recurrent ovarian cancer in first relapse who had low CA-125 levels. No new safety concerns were identified with the combination of FAR-CT. Since FAR binds to the folate receptor alpha, a novel antibody-drug conjugate has been developed and clinical studies are ongoing to assess the safety/efficacy of this modification. Clinical Trial Registry: NCT02289950

Japan Society of Gynecologic Oncology guidelines 2015 for the treatment of vulvar cancer and vaginal cancer

BackgroundVulvar cancer and vaginal cancer are relatively rare tumors, and there had been no established treatment principles or guidelines to treat these rare tumors in Japan. The first version of the Japan Society of Gynecologic Oncology (JSGO) guidelines for the treatment of vulvar cancer and vaginal cancer was published in 2015 in Japanese.ObjectiveThe JSGO committee decided to publish the English version of the JSGO guidelines worldwide, and hope it will be a useful guide to physicians in a similar situation as in Japan.MethodsThe guideline was created according to the basic principles in creating the guidelines of JSGO.ResultsThe guidelines consist of five chapters and five algorithms. Prior to the first chapter, basic items are described including staging classification and history, classification of histology, and definition of the methods of surgery, radiation, and chemotherapy to give the reader a better understanding of the contents of the guidelines for these rare tumors. The first chapter gives an overview of the guidelines, including the basic policy of the guidelines. The second chapter discusses vulvar cancer, the third chapter discusses vaginal cancer, and the fourth chapter discusses vulvar Paget’s disease and malignant melanoma. Each chapter includes clinical questions, recommendations, backgrounds, objectives, explanations, and references. The fifth chapter provides supplemental data for the drugs that are mentioned in the explanation of clinical questions.ConclusionOverall, the objective of these guidelines is to clearly delineate the standard of care for vulvar and vaginal cancer with the goal of ensuring a high standard of care for all women diagnosed with these rare diseases

Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer

Current status of gynecologic cancer in Japan

To make an overview of the current status of gynecologic cancer in Japan, we reviewed the recent incidence of cervical, endometrial, and ovarian cancer in Japanese women. The incidence of all three cancers has increased, but trends differ respectively. In age specific cancer site distribution data, the uterus and ovary are leading sites of high incidence among Japanese women younger than 40 years of age. Therefore, fertility sparing cancer treatment has received much attention. Several multicenter clinical trials have been done by Japanese groups, and some excellent evidence has been collected for endometrial and ovarian cancer. A promising international collaboration trial for ovarian clear cell carcinoma is also underway at the present time