Academic Journal
Once daily cediranib and weekly paclitaxel to prevent malignant bowel obstruction in at-risk patients with platinum-resistant ovarian cancer (CEBOC): a single-arm, phase II safety trial
| Τίτλος: | Once daily cediranib and weekly paclitaxel to prevent malignant bowel obstruction in at-risk patients with platinum-resistant ovarian cancer (CEBOC): a single-arm, phase II safety trial |
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| Συγγραφείς: | Alexander D Murphy, Catharine Porter, Ann White, Alys Irving, Richard Adams, Ruby Ray, Angela Casbard, Reem D Mahmood, Suman Karanth, Cong Zhou, Julia Pugh, Chelsey Wheeler, Victoria Roberts, Giorgio Arnetoli, Zena Salih, Jurjees Hasan, Claire Mitchell, Robert D Morgan, Andrew R Clamp, Gordon C Jayson |
| Πηγή: | AD, M, Porter, C, White, A, Irving, A, Adams, R, Ray, R, Casbard, A, Mahmood, R, Karanth, S, Zhou, C, Pugh, J, Wheeler, C, Roberts, V, Arnetoli, G, Salih, Z, Hasan, J, Mitchell, C, Morgan, R, Clamp, A & Jayson, G 2024, 'Once daily cediranib and weekly paclitaxel to prevent malignant bowel obstruction in at-risk patients with platinum-resistant ovarian cancer (CEBOC): a single-arm, phase II safety trial.', International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, vol. 34, no. 7, pp. 1034-1040. https://doi.org/10.1136/ijgc-2024-005455 |
| Στοιχεία εκδότη: | Elsevier BV, 2024. |
| Έτος έκδοσης: | 2024 |
| Θεματικοί όροι: | Adult, Indoles, Paclitaxel, Drug Resistance, Carcinoma, Ovarian Epithelial, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, Paclitaxel/administration & dosage, Antineoplastic Combined Chemotherapy Protocols, Humans, Carcinoma, Ovarian Epithelial/drug therapy, Aged, Ovarian Neoplasms, Antineoplastic Combined Chemotherapy Protocols/adverse effects, Carcinoma, Ovarian Neoplasms/drug therapy, Middle Aged, Quinazolines/administration & dosage, 3. Good health, Ovarian Epithelial/drug therapy, Drug Resistance, Neoplasm, Intestinal Obstruction/chemically induced, Quinazolines, Neoplasm, Female, Intestinal Obstruction |
| Περιγραφή: | Cytotoxic chemotherapy for ovarian cancer can be augmented by co-administration of vascular endothelial growth factor inhibitors but these are contraindicated in patients with bowel obstruction due to the risk of gastrointestinal perforation. We evaluated the safety and feasibility of paclitaxel plus cediranib to treat patients with platinum-resistant ovarian cancer at risk of malignant bowel obstruction.A phase II trial included eligible patients between March 2018 and February 2021, identified by clinical symptoms and radiographic risk factors for malignant bowel obstruction. Cediranib (20 mg/day) was added to paclitaxel (70 mg/m2/week) within 9 weeks of starting paclitaxel if pretreatment bowel symptoms had improved. The primary endpoint was the number of patients treated for ≥5 days with cediranib that were free of grade 3-5 gastrointestinal perforation or fistula. Secondary endpoints were hospitalization for bowel obstruction, grade ≥3 adverse events, treatment compliance assessed by relative dose intensity, objective response, progression-free survival, and overall survival.Thirty patients were recruited. Of these, 12 received paclitaxel alone and 17 received paclitaxel and cediranib in combination. One patient died before starting treatment. No patient developed a grade 3-5 gastrointestinal perforation or fistula (one sided 95% confidence interval (CI) upper limit 0.16). One patient required hospitalization for bowel obstruction but recovered with conservative management. The most common cediranib-related grade ≥3 adverse events were fatigue (3/17), diarrhorea (2/17), and hypomagnesemia (2/17). Relative dose intensity for paclitaxel was 90% (interquartile range (IQR) 85-100%; n=29) and for cediranib 88% (IQR 76-93%; n=17). The objective response in patients who received paclitaxel and cediranib was 65.0% (one complete and 10 partial responses). Median progression-free survival was 6.9 months (95% CI 4.4-11.5 months; n=17) and overall survival was 19.4 months (95% CI 10.1-20.4 months; n=17). Median follow-up was 12.4 months (8.9-not reached; n=17).The unexpectedly high withdrawal rate during paclitaxel alone, before introducing cediranib, meant we were unable to definitely conclude that paclitaxel plus cediranib did not cause gastrointestinal perforation or fistula. The regimen was however tolerated.EudraCT 2016-004618-93. |
| Τύπος εγγράφου: | Article |
| Γλώσσα: | English |
| ISSN: | 1048-891X |
| DOI: | 10.1136/ijgc-2024-005455 |
| Σύνδεσμος πρόσβασης: | https://pubmed.ncbi.nlm.nih.gov/38724236 https://research.manchester.ac.uk/en/publications/ce1b52c5-2554-4e13-926c-ba7fd010053c https://doi.org/10.1136/ijgc-2024-005455 https://research.manchester.ac.uk/en/publications/ce1b52c5-2554-4e13-926c-ba7fd010053c https://orca.cardiff.ac.uk/id/eprint/169252/1/ijgc-2024-005455.pdf https://doi.org/10.1136/ijgc-2024-005455 |
| Rights: | Elsevier Non-Commercial |
| Αριθμός Καταχώρησης: | edsair.doi.dedup.....0bcb8aaac244340a93a81653b0b207b9 |
| Βάση Δεδομένων: | OpenAIRE |
| ISSN: | 1048891X |
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| DOI: | 10.1136/ijgc-2024-005455 |