Hideo Omi

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/m2 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.

Neoadjuvant Chemotherapy Using Platinum-Based Regimens for Stage Ib2-II Squamous Cell Carcinoma and Non-Squamous Cell Carcinoma of the Cervix

The methods used for treating stage Ib2-IIb cervical cancers, with a bulky mass, differ between Japan and Western countries. In Western countries, concurrent chemoradiation (CCRT) has been recommended as a standard therapy for such tumors based on the results of multiple large-scale randomized trials and meta-analyses (Morris et al., 1999; Rose et al., 1999; Whitney et al., 1999; Pearcey et al., 2002; Eifel et al. 2004; Green et al. 2001; Lukka et al., 2002). In Japan, Korea, Italy and some other countries, the neoadjuvant chemotherapy (NAC) approach has been extensively introduced to clinical practice (Sugiyama et al., 1999). NAC is considered to be clinically significant in 2 respects: it is expected to improve the radicality and safety of surgery by reducing tumor size; and it is expected to exert systemic effects, i.e., effects on lymph node occult micrometastases, etc. A disadvantage of NAC is delayed initiation of the primary treatment, suggesting the necessity of completing NAC as an auxiliary therapy within a short period of time. Therefore, we may find that NAC is valuable if it can exert efficacy rapidly with high platinum dose intensity (DI), assuring that subsequent primary surgical therapy can be performed as soon as possible. At our facility, a platinum-based regimen has been used for NAC in patients with cervical cancer. Herein, we review the efficacy and safety data on NAC for squamous cell carcinoma of the uterine cervix. We previously reported our interim data and now present the results of an ongoing pilot study on the efficacy and safety of NAC for non-squamous cell carcinoma of the uterine cervix.

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.

Appendiceal mucocele and peritoneal inclusion cyst mimicking right adnexal masses: a diagnostic challenge in gynecologic practice

Mucocele of the appendix (MA) is an uncommon disease. Preoperative differential diagnosis of MA and a peritoneal inclusion cyst (PIC) from gynecologic diseases is still a challenge. We herein report a very rare case with MA and PIC. As far as we know, this is the first report of a case having MA and PIC found simultaneously at surgery. A 31-year-old woman complained of lower abdominal pain and high fever. Based on her symptoms and laboratory tests, pelvic inflammatory disease (PID) was considered to be the most probable diagnosis. She underwent antibiotics therapy and her conditions subsided. However, ascites reappeared in a month, and ultrasound and MRI demonstrated a right ovarian cyst and a suspected right hydrosalpinx. Laparotomy revealed large PIC and MA with normal bilateral adnexa. Patients with an adnexal mass or symptoms suggesting PID should be examined carefully considering such conditions in a daily gynecologic practice.

Safe administration of bevacizumab combination chemotherapy for the patients with recurrent cervical cancer after pelvic radiotherapy: Two case reports

In Japan, bevacizumab has not been proven either effective or safe for the treatment of recurrent cervical cancer. The present study reported two cases in which bevacizumab combination chemotherapy was safely administered for recurrent cervical cancer following pelvic radiotherapy. Case 1 was a 62-year-old woman with stage IIIB squamous cell carcinoma of the cervix who had received whole pelvic external beam radiotherapy (WPEBRT) at a dose of 50.4 Gy and high dose rate intra-cavitary brachytherapy at a dose of 24 Gy to the pelvis one year earlier. For recurrent cervical cancer, chemotherapy with paclitaxel, carboplatin and bevacizumab was administered for six cycles. Case 2 was a 52-year-old woman with stage IIB squamous cell carcinoma of the cervix who had received WPEBRT at a dose of 50.4 Gy to the pelvis 11 years earlier. For lymph node and liver metastases, chemotherapy with paclitaxel, cisplatin, and bevacizumab was administered for six cycles. Although grade 2 proteinuria was observed in one of these patients, there were no intestinal perforation, fistula, hypertension, proteinuria or thrombosis events, which are the characteristic adverse reactions associated with bevacizumab. Hematotoxicity was also manageable. Regarding the antitumor effect, case 1 demonstrated a complete response, whereas case 2 resulted in stable disease.

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.

A retrospective study of neoadjuvant chemotherapy plus radical hysterectomy versus radical hysterectomy alone in patients with stage II cervical squamous cell carcinoma presenting as a bulky mass

Objective In order to evaluate the usefulness of neoadjuvant chemotherapy (NAC) for stage II cervical squamous cell carcinoma with a bulky mass, we retrospectively compared patients receiving NAC followed by radical hysterectomy (RH; NAC group) with patients who underwent RH without NAC (Ope group). Patients and methods The study period was from June 2002 to March 2014. The subjects were 28 patients with a stage II bulky mass in the NAC group and 17 such patients in the Ope group. The chi-square test was used to compare operative time, volume of intraoperative blood loss, use of blood transfusion, and time from surgery to discharge between the two groups. Moreover, the log-rank test using the Kaplan–Meier method was performed to compare disease-free survival (DFS) and overall survival (OS) between the groups. Results There were no statistically significant differences between the two groups in operative time, volume of intraoperative blood loss, or use of blood transfusion. However, the time from surgery to discharge was 18 days (14–25 days) in the NAC group and 25 days (21–34 days) in the Ope group; the patients in the NAC group were discharged earlier (P=0.032). The hazard ratio for DFS in the NAC group as compared with that in the Ope group was 0.36 (95% CI 0.08–0.91), and the 3-year DFS rates were 81.2% and 41.0%, respectively (P=0.028). Moreover, the hazard ratio for OS was 0.39 (95% CI 0.11–1.24), and the 3-year OS rates were 82.3% and 66.4%, respectively (P=0.101). Conclusion NAC with cisplatin and irinotecan was confirmed to prolong DFS as compared with RH alone. The results of this study suggest that NAC might be a useful adjunct to surgery in the treatment of stage II squamous cell carcinoma presenting as a bulky mass.