Determining the maximum tolerated dose of paclitaxel combined with fixed dose of cisplatin for hyperthermic intraperitoneal chemotherapy in ovarian cancer: A multicenter phase I trial.

OBJECTIVE: To determine the maximum tolerated dose (MTD) of paclitaxel combined with a fixed dose of cisplatin (75 mg/m2) delivered via hyperthermic intraperitoneal chemotherapy (HIPEC) to patients with ovarian cancer. METHODS: This multicenter Phase I trial employed a Bayesian Optimal Interval (BOIN) design. The MTD was determined to have a target dose-limiting toxicity (DLT) rate of 25%. The starting dose was 175 mg/m2. The Data and Safety Monitoring Board made decisions regarding dose escalation or de-escalation in increments of 25 mg/m2 for subsequent patient cohorts, up to a maximum sample size of 30 or 12 patients treated at a given dose. RESULTS: Twenty-one patients participated in this study. Among the three evaluable patients who received 150 mg/m2 paclitaxel, no DLTs were observed. Among the 12 evaluable patients who received 175 mg/m2 paclitaxel, two reported DLTs: one had grade 4 neutropenia and one had grade 4 anemia, neutropenia, and leukopenia. Four of the six evaluable patients who received 200 mg/m2 paclitaxel reported DLTs: one patient had grade 4 diarrhea, one had grade 3 kidney injury, and two had grade 4 anemia. The isotonic estimate of the DLT rate in the 175 mg/m2 dose group was 0.17 (95% confidence interval, 0.02-0.42), and this dose was selected as the MTD. CONCLUSION: Paclitaxel, when combined with a fixed dose of cisplatin (75 mg/m2), can be safely administered intraperitoneally at a dose of 175 mg/m2 in patients with ovarian cancer who received HIPEC (43 °C, 90 min) following cytoreductive surgery.

Efficacy of neoadjuvant hyperthermic intraperitoneal chemotherapy in advanced high-grade serous ovarian cancer (the NHIPEC trial): study protocol for a randomised controlled trial.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is an important treatment option for patients with ovarian cancer. Although intravenous NACT can improve optimal resection rates and decrease surgical morbidity and mortality, these advantages do not translate into a survival benefit. Ovarian carcinoma is mainly confined to the peritoneal cavity, which makes it a potential target for hyperthermic intraperitoneal chemotherapy (HIPEC). Our previous study showed that HIPEC could be used in the neoadjuvant setting, which was named neoadjuvant HIPEC (NHIPEC). Since hyperthermia is an excellent chemosensitiser, we hypothesised that the combination of NHIPEC and intravenous NACT could show superior efficacy to intravenous NACT alone. METHODS: This study is a single-centre, open-label, randomised (1:1 allocation ratio) phase 2 trial. A total of 80 patients will be randomly assigned into an experimental group (NHIPEC+intravenous NACT) or a control group (intravenous NACT). Patients in the experimental group will receive NHIPEC following laparoscopic evaluation, and four tubes will be placed via the laparoscopic ports, which will be used to administer NHIPEC. Then, perfusion with docetaxel (60-75 mg/m2) will be performed (43°C for 60 min, Day 0) followed by cisplatin (75 mg/m2, Day 1) infusion (43°C for 60 min) 24 hours later. After NHIPEC, two cycles of intravenous NACT will be given. Patients in the control group will receive three cycles of intravenous NACT. The primary endpoint is the proportion of patients who achieve a Chemotherapy Response Score (CRS) of 3 according to the CRS system. The secondary endpoints include progression-free survival, overall survival and the rates of complete resection and NHIPEC-related adverse events. ETHICS APPROVAL AND DISSEMINATION: This study was approved by the Ethics Committee of Sun Yat-sen Memorial Hospital (approval number: 2020-ky-050). Results will be submitted to peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000038173.

Neoadjuvant chemotherapy with paclitaxel plus platinum for invasive cervical cancer in pregnancy: two case report and literature review.

BACKGROUND: Cervical cancer (including carcinoma in situ) is the most common malignancy during pregnancy. Neoadjuvant chemotherapy (NACT) with paclitaxel plus cisplatin has been used in patients with cervical cancer successfully, but experience of its prenatal treatment is limited. CASE REPORT: We report two pregnant women with locally advanced cervical cancer. They were treated with cisplatin plus paclitaxel NACT until fetal pulmonary maturity was achieved, and then accepted cesarean section followed by radical hysterectomy. To minimize the chemo-resistant/radio-resistant tumor cell clones and increase the potencies of NACT, we modified the dose of the chemotherapeutic agents and the treatment interval using cisplatin (50 mg/m(2)) and paclitaxel (75 mg/m(2)) every 2 weeks. Evaluation for clinical response to chemotherapy displayed a partial and complete response, respectively. Both patients had not had any evidence of recurrence for 21 and 13 months. Their children did not have any evidence of malformations and showed normal development at 21 and 13 months of follow-up, respectively. CONCLUSION: Neoadjuvant chemotherapy with paclitaxel plus cisplatin appears to be feasible and safe for pregnant patients with invasive cervical cancer and infants.

[Influences of lymphatic vessel ligation in pelvic lymphadenectomy on postoperative lymphocyst formation--a randomized controlled trial].

BACKGROUND AND OBJECTIVE: Pelvic lymphocysts are the most common postoperative complications of pelvic lymphadenectomy. Prevention of this disease is more important than treatment. This randomized study was to evaluate the preventive effect of lymph vessel ligation during pelvic lymphadenectomy on pelvic lymphocyst formation. METHODS: A total of 39 patients with gynecologic malignancy, who had pelvic lymphadenectomy in the Second Affiliated Hospital of Sun Yat-sen University from July 2006 to January 2007, were randomized into the ligation group (19 patients) and the non-ligation group (20 patients). All patients had no heart disease, hepatopathy, nephronia, pneumonopathy, hypoproteinemia and no history of radiotherapy. All the patients were followed-up with sonographic evaluation and physical examination for lymphocysts and other postoperative complications at 1, 4, 12, and 24 weeks after operation. RESULTS: No significant differences were observed between the two groups in pathlogic type, age, height, weight, body surface area, body mass index (BMI), operation duration, estimated blood loss, time to the passage of flatus, total drainage volume, duration of drainage, and duration of hospital stay (P>0.05). The occurrence rate of lymphocysts was significantly lower in the ligation group than in the non-ligation group at one week after operation (26.3% vs. 60.0%, P<0.05). The rates were slightly lower in the ligation group than in the non-ligation group without significant differences after then (31.6% vs. 55.0% at the 4th week), (16.7% vs. 45.0% at the 12th week), (20.0% vs. 27.8% at the 24th week). No significant differences were observed in the occurrence of other postoperative complications between the two groups (P<0.05). CONCLUSION: Ligations of the deep inguinal lymph vessels, obturator lymph vessels, common iliac lymph vessels, and the lymph vessels at the crossing of the external iliac and the inter iliac vein can decrease the occurrence of postoperative lymphocysts in short-term period, and will not increase the occurrence of postoperative complications.

[Construction of adeno-associated virus vector containing human papilloma virus 16 E7 gene and its expression in eukaryotic cells].

OBJECTIVE: To construct recombinant adeno-associated virus vector containing human papilloma virus (HPV) 16E7 gene and identify its effectiveness of expression in eukaryotic cell. METHODS: Recombinant adeno-associated virus particles containing HPV16E7 gene were generated by co-transfection of plasmids pAAV-MCS-E7, pAAV-RC and pAAV-helper into HEK293 cells. The viral particles were collected and purified. The vector titer was measured by southern blot. After the eukaryotic cells were transfected by virus particles, RT-PCR and western blot analysis were performed to identify rAAV expression. RESULTS: The recombinant adeno-associated virus vector containing HPV16E7 gene was correctly constructed. The vector titer measured by southern blot was approximately 1 x 10(11)/ml. After the eukaryotic cells were transfected by the recombinant adeno-associated virus vector, the expression of HPV16E7 gene was identified by RT-PCR and western blot. CONCLUSIONS: Recombinant adeno-associated virus HPV16E7 vector is successfully constructed and can stably express in eukaryotic cells.