Combination chemotherapy with irinotecan and gemcitabine for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancer: a multicenter phase I/II trial (GOGO-Ov 6).

PURPOSE: To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy. METHODS: Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m2, respectively; level 2: 100 and 1000 mg/m2) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity. RESULTS: A total of 35 patients were enrolled. The recommended dose was defined as 100 mg/m2 irinotecan and 1000 mg/m2 gemcitabine (level 2). The observed common grade 3/4 toxicities were neutropenia (60%), anemia (17.1%), diarrhea (8.6%), thrombocytopenia (5.7%) and nausea (5.7%). Groups homozygous for UGT1A1*6 or *28 were associated with grade 3/4 neutropenia and diarrhea. Objective responses were 20%, including one complete response and six partial responses. In 29 patients treated with the recommended dose, the median progression-free survival and overall survival were 3.8 months (95% CI 2.1-6.0 months) and 17.4 months (95% CI 9.9-21.9 months), respectively, while the 1-year survival rate was 58.6%. CONCLUSIONS: Combination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.

[Curative Resection for Metastatic Lower Rectal Tumor from Ovarian Cancer - Report of a Case].

We here report the case of a 56-year-old female patient who underwent curative resection for right ovarian cancer with intraperitoneal dissemination and liver metastases. She received following adjuvant chemotherapy, and had been visited hospital for regular follow-up since then. One and half a year after surgery, blood examination showed increasing value of CA125. Contrast-enhanced CT scan revealed a tumor whose long diameter was 5 cm at front side of lower rectum. Following MRI and PET-CT examinations indicated the pelvic tumor as recurrence of ovarian cancer, so that laparotomy was carried out. As the tumor was palped through Douglas cavum, we performed low-anterior rectal resection for en bloc tumor extirpation. Tumor cells mainly developed at peri-rectal wall and proper muscle by HE staining of pathological findings, and ER(positive), vimentin(positive), CD56(positive), synaptophysin(negative)and chromogranin A(negative)by immunostaining indicated the tumor as metastasis of ovarian cancer. Though rectal metastasis from ovarian cancer is basically rare, it might be necessary to rule out possibility of metastatic colon tumor from ovarian cancer when treating patient with rectal tumor who had underwent surgery for ovarian cancer before.

Chemotherapy for endometrial carcinoma (GOGO-EM1 study): TEC (paclitaxel, epirubicin, and carboplatin) is an effective remission-induction and adjuvant therapy.

BACKGROUND: TAP chemotherapy (paclitaxel, doxorubicin, and cisplatin) is effective for advanced and recurrent endometrial carcinoma, but has occasional severe toxicity. TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determined. PATIENTS AND METHODS: Phase I/II prospective study for TEC therapy was performed. A retrospective comparison of the prognosis between adjuvant TEC therapy and radiation for completely resected cases with risk factors was also performed. RESULTS: The recommended dose of TEC therapy was determined to be paclitaxel 150 mg/m(2), epirubicin 50 mg/m(2), and carboplatin AUC 4. A TEC regimen at this dose level was shown to be tolerable. The response rate and median overall survival were 74% and 37 months for those with advanced primary disease (Group B) and 50% and 26 months for recurrent tumors (Group C), respectively. A retrospective comparison showed that adjuvant TEC therapy for completely resected stage III cases improved their prognosis when compared to an adjuvant radiation therapy. CONCLUSION: TEC therapy was demonstrated to be a tolerable and effective treatment, not only as a remission-induction therapy for advanced and recurrent endometrial carcinomas but also as the adjuvant therapy.

Prognostic significance of p53 mutation in suboptimally resected advanced ovarian carcinoma treated with the combination chemotherapy of paclitaxel and carboplatin.

The prognostic significance of p53 mutation, microsattelite instability and DNA mismatch protein hMLH1 expression in suboptimally resected advanced ovarian carcinoma treated with the combination chemotherapy of paclitaxel and carboplatin was evaluated. The overall combination chemotherapy response rate and the complete remission rate were significantly higher among patients with mutant p53 tumors than those with wild-type p53 tumors (35/42 (83%) vs. 32/58 (55%); P=0.003 and 18/42 (43%) vs. 16/58 (28%); P=0.03, respectively). This tendency apparently existed in non-serous carcinoma, but not in serous carcinoma. Univariate analysis showed that the risk of death due to disease and risk of progression was significantly lower among patients with p53 mutation (P=0.0357 and 0.0281, respectively). However, the presence of microsattelite instability or loss of hMLH1 expression was not associated with either the clinical response or prognosis. Determining p53 mutational status can be useful in predicting therapeutic response to drugs in ovarian carcinoma, especially in non-serous tumors.