A Randomised Phase ii Trial in Advanced Epithelial Ovarian Cancer (Eoc), With Prospective Translational End-Points to Predict Chemotherapy Response (Ctcr-Ov01)
- Abstract:
- Patients (pts) were consented for diagnostic and fresh tissue research biopsies, and randomised (1:1) to: Arm A Carboplatin AUC 7 every 3 weeks (C) x 3 cycles (cy); interval debulking surgery (IDS); followed by C AUC 6 with paclitaxel 175mg/m2 q 3w (CT) x 3cy; and finally paclitaxel 175 mg/m2 q3w (T) x 3cy; or Arm B T x 3cy; IDS; CT x 3cy; C x 3cy. At IDS further fresh tissue samples were collected. Clinical Endpoints: (i) Partial response rate for CA125 (CA125 RR) and CT scan (CT RR). (ii) Median progression-free survival (PFS). Translational endpoints: Candidate genes and molecular profiles as predictive markers of response/resistance to C and T. Results Jan’02-Dec’04, 44 pts were randomised (21ptsA / 23ptsB). Median age 60yr (range 36-75yrs); 42/44 serous papillary histology; stage III/IV = 77%/23%; grade I/II/III = 2%/34%/64%. Significant toxicity (G3-4) was more common with Arm B, as were chemotherapy delays (A10.6%: B14.6%). Median follow-up is 22 months (IQR 17-33.5). CA125 RR to pre-operative chemotherapy was A/B = 65%/60% (p = 1). CT RR was A/B = 47%/35% (p = 0.15). CA125 responders had PFS 17.3m v 12.4m for non-responders, p = 0.027. Median PFS was 14months(m) (A/B=13m/14m (p = 0.53)). Supervised analysis of Affymetrix expression data showed significant enrichment for differential extra-cellular gene expression in paclitaxel resistant patients. Conclusions Prospective controlled randomized trials using neoadjuvant treatment are ideally suited for translational research in EOC and provide unique sample sets for informative molecular analysis.
- Authors:
- AA Ahmed, A-L Vallier, C Parkinson, M Iddawela, J Latimer, R Crawford, JD Brenton, HM Earl
- Journal:
- International Journal of Gynecological Cancer
- Citation info:
- 16:668
- Publication date:
- 1st Oct 2006
- Full text
- DOI