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.

Phase II clinical study of neoadjuvant chemotherapy with CDDP/CPT-11 regimen in combination with radical hysterectomy for cervical cancer with a bulky mass.

BACKGROUND: We examined the efficacy and safety of neoadjuvant chemotherapy (NAC) with the CPT-11 + CDDP regimen in combination with radical hysterectomy. SUBJECTS AND METHODS: The subjects were 42 patients with stages IB2 to IIIB squamous cell carcinoma of the uterine cervix with a bulky mass. CDDP at 70 mg/m2 was intravenously administered on day 1 and CPT-11 at 70 mg/m2 was intravenously administered on days 1 and 8 of a 21-day cycle. In principle, two cycles were administered followed by radical hysterectomy. We examined antitumor efficacy, adverse events, completion rate of radical hysterectomy, operative time, surgical blood loss, progression-free survival (PFS), and overall survival (OS). RESULTS: The antitumor effect was complete response in 7 patients, partial response in 28, stable disease in 6, and progressive disease in 1; the response rate was 83.3 % (95 % confidence interval, 68.6-93.0). Grade 3 or more severe neutropenia, anemia, and platelet count decreases were noted in 23 (54.8 %), 4 (9.5 %), and 1 (2.4 %) patient, respectively. Grade 3 nausea occurred in 3 patients (7.1 %), vomiting in 1 (2.4 %), and grade 3 febrile neutropenia in 2 (7.1 %). The completion rate of radical hysterectomy was 88.1 %. The median operative time and surgical blood loss were 260 min (range, 210-334) and 500 ml (range, 393-898), respectively. The 5-year PFS rate was 67.2 %, and the 5-year OS rate was 68.0 %. In multivariate analysis, lymph node metastasis before NAC [hazard ratio (HR), 34.88] and non-response to NAC (HR 30.58) were significant prognostic factors. CONCLUSION: NAC with the CDDP/CPT-11 regimen achieves a high antitumor efficacy with moderate adverse reactions, allowing safe radical hysterectomy, and is thus considered to be a useful therapeutic method that can improve prognosis.

A phase II clinical trial of palonosetron for the management of delayed vomiting in gynecological cancer patients receiving paclitaxel/carboplatin therapy.

There are currently no studies demonstrating the effects of palonosetron on delayed chemotherapy-induced nausea and vomiting (CINV) in gynecological cancer patients receiving chemotherapy with moderately emetogenic chemotherapeutic agents. We conducted a phase II clinical trial to assess the efficacy and safety of palonosetron in patients receiving paclitaxel/carboplatin (TC) therapy. The study population consisted of 42 patients who had been diagnosed with gynecological malignancies and treated with TC. On day 1, 0.75 mg/body palonosetron and 19.8 mg/body dexamethasone were administered intravenously immediately prior to TC therapy. Dexamethasone in daily doses of 6.6 mg/body was also administered intravenously on days 2 and 3. The efficacy and safety of palonosetron + dexamethasone were evaluated by the self-completion method using the Multinational Association of Supportive Care in Cancer Antiemesis Tool during an observation period lasting from day 1 through day 8 of the initial cycle of TC therapy. The severity of the nausea was assessed using a visual analog scale. During the acute (0-24 h), delayed (24-96 h) and overall (0-96 h) periods, the complete response rates were 95.2, 90.5 and 85.7%, respectively, whereas the complete control rates were 90.5, 85.7 and 78.6%, respectively. Grade ≥ 2 constipation and diarrhea developed in 1 patient (2.4%) each. The palonosetron + dexamethasone regimen proved to be effective for delayed CINV in gynecological cancer patients receiving TC therapy. This combined antiemetic regimen was associated with only mild adverse reactions and may serve as supportive therapy, allowing cancer chemotherapy to be continued while maintaining an adequate quality of life.

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.

Effective use of everolimus as salvage chemotherapy for ovarian clear cell carcinoma: a case report.

A case study using mammalian target of rapamycin complex 1 in recurrent ovarian clear cell carcinoma (CCC) was recently conducted. We report our experience with a patient suffering from recurrent ovarian CCC who achieved long-term disease control with everolimus administration. The patient was a 53-year-old woman who was diagnosed with recurrent ovarian CCC with dissemination throughout the abdominal cavity. Previously, she had received three chemotherapy regimens, but the disease was progressive and she showed no response to treatment. Therefore, oral everolimus administration (everolimus 10 mg/day on days 1-28, a 28-day period comprised one cycle) was started. She was administered six cycles. The antitumor response was stable disease, and grade 3 anemia was observed. Chemotherapy was then switched to gemcitabine/docetaxel therapy. In the middle of the second cycle, a rapid increase in ascitic fluid and CA125 elevation were observed. Thereafter, the patient received best supportive care and died of the disease. Everolimus may inhibit malignant progression of ovarian CCC.

A pilot study of oxaliplatin with oral S-1 as second-line chemotherapy for patients with recurrent adenocarcimona of the uterine cervix.

BACKGROUND: The efficacy and safety of S-1/oxaliplatin (SOX) therapy in patients with recurrent adenocarcinoma of the uterine cervix were examined in a pilot study. PATIENTS AND METHODS: S-1 was orally administered for 14 days at a dose of 80-120 mg/body/day to 7 patients with recurrent adenocarcinoma of the uterine cervix, with oxaliplatin being administered intravenously at a dose of 100 mg/m(2) on day 1. Each therapy cycle was 21 days, and the patients received 6 cycles at most. The antitumor effect, adverse events, progression-free survival (PFS), and overall survival (OS) were investigated. RESULTS: The median age of the patients was 49 years. The antitumor effect was rated as a complete response in 2 patients, partial response in 2, and stable disease in 3. The overall response rate was 57.1 %, and the disease control rate was 100 %. Regarding hematological toxicities of grade 3 or more, leukopenia, neutropenia and thrombocytopenia occurred in 42.9, 28.6 and 14.3 %, respectively; regarding non-hematological toxicities, grade 3 rectovaginal fistula occurred in 14.3 %, as well as grade 2 fatigue in 14.3 % of the patients. The median PFS and OS were 5 months (range 3-9 months) and 7 months (range 4-43 months), respectively. CONCLUSIONS: These results suggest that SOX therapy is useful for the treatment of recurrent adenocarcinoma of the uterine cervix, having a promising antitumor effect and minimal adverse effects. It was also suggested that SOX therapy may contribute to improving the prognosis for patients with adenocarcinoma of the uterine cervix.

[Ovarian cancer-criteria of response and the timing of regimen change in chemotherapy for ovarian cancer].

Recently, the resistant-to-paclitaxel/carboplatin therapy(TC), the standard first-line chemo-regimen for epithelial ovarian cancer(EOC), has been reported in subtypes of EOC, such as clear cell carcinoma and mucinous adenocarcinoma. The response to the chemo-regimen is evaluated by tumor markers and imaging of CT/MRI. The timing of regimen change depends on the identification of progressive disease(PD), using Rustin's criteria for CA125 and RECIST v1.1 for imaging, or severe adverse events(AEs>=grade 3, 4)in non-hematologic toxicities. For patients with refractory or recurrent EOC, the aim of their treatment was changed to keeping their quality of life for as long as possible with/without curing them from the disease. Thus, the selection of regimens for recurrent EOC should be suitable for the patient-friendly regimens, such as those with fewer AEs, out-patient- setting and shorter administration. As for molecular-targeted agents, bevacizumab and olaparib with TC therapy were reported to give patients significantly longer progression-free survival than control arms. Further investigation of immune-therapy or new agents for aiming total cell kill of tumor cell is should be warranted to obtain longer overall survival in patients with advanced EOC.

Objective evaluation of the alleviating effects of Goshajinkigan on peripheral neuropathy induced by paclitaxel/carboplatin therapy: A multicenter collaborative study.

Paclitaxel/carboplatin chemotherapy for cancer (TC therapy) exhibits neurotoxicity and causes peripheral neuropathy at a high frequency, which is difficult to cope with. In this study, we investigated the efficacy of Goshajinkigan, a traditional Japanese herbal medicine, for TC therapy-induced peripheral neuropathy. The subjects included in our study were patients with ovarian or endometrial cancer who underwent TC therapy and developed peripheral neuropathy. The patients were randomly divided into Group A, comprising of 14 patients (vitamin B12 treatment), and Group B, comprising of 15 patients (vitamin B12 + Goshajinkigan treatment). The observation period was 6 weeks following treatment initiation, and the evaluation items were as follows: i) the current perception threshold (CPT value) of the peripheral nerve, ii) visual analogue scale for numbness, iii) National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grade of neurotoxicity, and iv) a questionnaire on the subjective symptoms of peripheral neuropathy (functional assessment of cancer therapy-taxane). These were compared between the groups and no significant differences were noted in any item. However, CTCAE grade 3 neurotoxicity developed in 2 patients (14.3%) after 6 weeks of administration in Group A, whereas no neurotoxicity was observed in Group B. When the change in the frequency of abnormal CPT ratio at 6 weeks of administration from that before treatment was compared between the groups, the frequency of abnormal value was significantly lower in Group B than in Group A (p<0.05). This suggests that Goshajinkigan inhibits the progression of peripheral neuropathy.

Expression of human telomerase reverse transcriptase and correlation with telomerase activity in placentas with and without intrauterine growth retardation.

BACKGROUND: Human telomerase reverse transcriptase has been found in telomerase-positive tumor tissues, but not in telomerase-negative nonmalignant somatic cells. METHODS: Thirty-two first-trimester chorionic villi specimens (Group A), 33 second- and third-trimester placenta specimens without asymmetric intrauterine growth retardation (Group B) and 13 specimens of placenta tissue from cases with intrauterine growth retardation (Group C) were examined for telomerase activity and expression of human telomerase reverse transcriptase by reverse transcription polymerase chain reaction and quantitative reverse transcription polymerase chain reaction. RESULTS: Telomerase activity was detected in 29 of the 32 specimens (90.6%) in Group A, in 20 of the 33 specimens (60.6%) in Group B and none of the 13 specimens (0.0%) in Group C. Human telomerase reverse transcriptase was identified in all 32 specimens of Group A (100%), all 33 specimens of Group B (100%) and 2 of the 13 specimens in Group C (15.4%) by nested reverse transcription polymerase chain reaction. Copy numbers of human telomerase reverse transcriptase were 202.3 +/- 73.0 (n=32), 8.8 +/- 2.9 (n=33) and 0 (n=13) in Groups A, B, and C, respectively. Significant differences were observed between Groups A and B, Groups A and C, and Groups B and C (p <0.01, p < 0.01, and p < 0.01, respectively). CONCLUSIONS: Our findings indicate that human telomerase reverse transcriptase expression is the rate-limiting determinant of telomerase activity in chorionic villi during the first trimester. Telomerase activity was not detected in placentas with intrauterine growth retardation, whereas human telomerase reverse transcriptase was expressed in some placentas with intrauterine growth retardation.