[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.

[Treatments of epithelial ovarian cancer by histologic subtype].

Recent molecular studies support the hypothesis that clear cell carcinoma and mucinous adenocarcinoma are refractory cancers that are biologically distinct from serous adenocarcinoma. Treatment of these cancers has not yet been adequately tested, so separate clinical trials are needed for each type. Paclitaxel(175 mg/m2/3hr)combined with carboplatin AUC 6(TC regimen)is the current gold standard for treating ovarian cancer. Clear cell carcinoma and mucinous adenocarcinoma are less sensitive to a TC regimen than serous adenocarcinoma, and an international randomized trial for clear cell carcinoma is now underway(GCIG/JGOG3017). Targeted therapy is attractive for chemoresistant clear cell carcinoma, thus VEGFR inhibitor(sunitinib), PDGFR inhibitor(sorafenib), m-TOR inhibitor (temsirolimus), and monoclonal antibody(bevacizumab)are being evaluated. Mucinous adenocarcinoma often shows CK20- and CEA-positive patterns in immunohistochemistry, and furthermore, p53-negative and K-ras-positive in molecular markers, which suggests that mucinous adenocarcinoma resembles colorectal, stomach, and pancreas cancers more than serous ovarian adenocarcinoma. Trials are needed to test the agents effective for gastrointestinal cancer. The GOG will start a randomized phase III trial comparing TC regimen with capecitabine plus oxaliplatin(GOG241). We are starting a phase II study of S-1 plus oxaliplatin in Japan. For refractory cancers, molecular biology-based, cross- organ treatment with cytotoxic/cytostatic agents is needed.

[Ovarian cancer treatment from the standpoint of the gynecologic oncologist].

Ovarian cancer treatment on the standpoint of the gynecologic oncologist: Ovarian cancer is comprehensively treated with combined surgery and anticancer chemotherapy, which influence each other. In the initial surgery, a cancer stage is decided, and in advanced cancer, primary debulking surgery is conducted. The outcome of postoperative chemotherapy has a correlation with the diameter of the postoperative residual tumor. Recently, a new treatment strategy of interval debulking surgery during chemotherapy has been widely conducted to completely remove tumors. Improved diagnostic imaging such as PET enhances aggressive surgery for recurrent cancer.

Phase II study of tri-weekly cisplatin and irinotecan as neoadjuvant chemotherapy for locally advanced cervical cancer.

The present study aimed to assess the antitumor response and safety of a tri-weekly neoadjuvant chemotherapy regimen consisting of cisplatin and irinotecan for the treatment of locally advanced cervical cancer with a bulky mass. Between June 2002 and March 2008, 20 patients with locally advanced squamous cell carcinoma of the uterine cervix at clinical stage Ib2-IIIb were studied. Two 21-day cycles consisting of intravenous administration of cisplatin at 70 mg/m(2) (Day 1) and irinotecan at 70 mg/m(2) (Days 1 and 8) were performed. Antitumor responses, adverse events and the surgery completion rate were investigated. The response rate of the 15 stage I-II patients was 86.7%, while that of the 5 stage III patients was 20%. Grade 3 or 4 neutropenia was noted in 12 patients, and 4 patients had grade 3 or 4 anemia. Queasiness and vomiting, as grade 3 or 4 non-hematotoxic events, occurred in 1 patient, but none of the patients had diarrhea. The surgery completion rate was 75%. The present data indicate that the tri-weekly cisplatin and irinotecan combination neoadjuvant chemotherapy involves only controllable toxicity and yields a high response rate, suggesting that this combination is a useful therapy regimen.