ABSTRACT
PURPOSE: Low-dose fractionated whole abdominal radiation therapy (LDFWART) has synergistic activity with paclitaxel in preclinical models. The aim of this phase 1 trial was to determine the recommended phase 2 dose and preliminary activity of weekly paclitaxel (wP) concurrent with LDFWART in patients with platinum-resistant ovarian cancer (PROC). METHODS AND MATERIALS: Patients were enrolled at de-escalating dose levels of wP (part A), starting at 80 mg/m2, concurrent with fixed-dose LDFWART delivered in 60 cGy fractions twice-daily, 2 days per week, for 6 continuous weeks. After completing the 6-week course of wP + LDFWART, patients received wP until disease progression. Dose-limiting toxicity was evaluated during the first 3 weeks of wP + LDFWART. At wP (80 mg/m2) + LDFWART, no dose-limiting toxicities were observed; this was the established maximum tolerated dose. The trial was expanded (part B) with 7 additional patients with platinum-resistant, high-grade serous ovarian cancer to confirm toxicity and activity. RESULTS: A total of 10 heavily pretreated patients were recruited (3 patients to part A, 7 patients to part B). They had received a median of 5 prior lines of therapy, and 70% of patients had received prior wP; 60% of patients completed 6 weeks of wP + LDFWART. Common related grade ≥3 adverse events were neutropenia (60%) and anemia (30%). Median progression-free survival was 3.2 months, and overall survival was 13.5 months. Of patients evaluable for response, 33% (3 of 9) achieved confirmed biochemical response (CA125 decrease >50% from baseline), 11% (1) achieved a partial response, and 5 patients had stable disease, giving a disease control rate of 66.7% (6 of 9). Four patients had durable disease control of ≥12 weeks, completing 12 to 21 weeks of wP. CONCLUSIONS: The recommended phase 2 dose of wP + LDFWART for 6 weeks is 80 mg/m2. Encouraging efficacy in heavily pretreated PROC patients was observed, suggesting that further development of this therapeutic strategy in PROC should be considered.
Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Chemoradiotherapy/methods , Ovarian Neoplasms/therapy , Paclitaxel/administration & dosage , Abdomen , Adult , Aged , Anemia/chemically induced , Antineoplastic Agents, Phytogenic/adverse effects , Disease Progression , Dose Fractionation, Radiation , Drug Administration Schedule , Drug Resistance, Neoplasm , Female , Humans , Maximum Tolerated Dose , Middle Aged , Neutropenia/etiology , Ovarian Neoplasms/mortality , Paclitaxel/adverse effects , Patient Reported Outcome Measures , Platinum Compounds/therapeutic use , Progression-Free SurvivalABSTRACT
OBJECTIVE: Waterbirth has been increasing in popularity in Asia (Lea W. Water babies. The Straits Times 17 February 2011. Available at http://www.nuh.com.sg/news/media-articles_1504.html). National University Hospital, Singapore, is the pioneer hospital offering waterbirths to women since 2006 in a unique setting of a consultant-led service and continuous foetal monitoring. To date, no studies have been done on the conduct of waterbirths in an Asia. This study aims to evaluate if water immersion during delivery is associated with increased rates of adverse maternal and foetal outcomes as compared with conventional vaginal deliveries. MATERIALS AND METHODS: Clinical records of women who birthed underwater at National University Hospital between 2010 and 2013 were retrospectively reviewed. Outcomes of interest were estimated blood loss, third- or fourth degree tears, incidence of postpartum infections or haemorrhage, neonatal Apgars at 1 and 5 min, and neonatal complications requiring intensive care unit admission. Outcomes were compared against a matched control group of women who had conventional vaginal deliveries within ≤1 month. RESULTS: Records of 118 women who birthed underwater were accrued. There was no significant difference in estimated blood loss and postpartum haemorrhage between groups, and there were no cases of maternal infection, third- or fourth-degree perineal tears, or adverse neonatal outcomes in either group. Women in the control group were more likely to have episiotomies (63.6% vs. 0.85%; p < 0.01). Three cases of retained placenta were reported in the waterbirth group (0.03%). CONCLUSION: Waterbirth at our centre does not appear to be associated with an increased incidence of adverse neonatal and maternal outcomes. The results of this study supported waterbirth as a birthing option to groups of low-risk women in an obstetrician-led setting with good midwifery support.
