1 / 25

Chemoradiation for Locally Advanced Cervical Cancer- what next?

Chemoradiation for Locally Advanced Cervical Cancer- what next?. Mary McCormack & Jonathan Ledermann NCRI Gynae Clinical Studies Group. The current status- LACC. CRT standard of care for the past decade Meta- analysis 18 RCT in CRT (Vale et al 2008)

saxton
Download Presentation

Chemoradiation for Locally Advanced Cervical Cancer- what next?

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Chemoradiation for Locally Advanced Cervical Cancer- what next? Mary McCormack & Jonathan Ledermann NCRI Gynae Clinical Studies Group

  2. The current status- LACC • CRT standard of care for the past decade • Meta- analysis 18 RCT in CRT (Vale et al 2008) -absolute survival benefit of 6% at 5 years - all groups benefitted 7-10% stage I-II 3% stage III-IV

  3. Current Status • Overall survival with CRT 66% at 5years (Vale 2008) – but DFS only 58% • However – in those with : positive LN large volume tumours advanced stage outcome remains poor

  4. Neo-adjuvant /Induction chemotherapy -Rationale • Downstage • Eradicate micrometastases • Impact on survival ? Chemotherapy : short cycle interval 7% improvement in 5 year OS (Tierney 2003)

  5. CX II Study • Phase II single arm NCRI feasability study • Aim to assess response rate and toxicityof a short course of dose dense weekly chemotherapy prior to definitive chemoradiation in women with LACC

  6. Why weekly treatment ? • Dose dense schedules- enhanced cell kill ? overcome accelerated repopulation ? • Greater dose intensity (v q 3-weekly) • Well tolerated in head & neck / ovarian cancer patients

  7. Eligibility Criteria • Histologically confirmed FIGO stage Ib2- IVa (Squamous, Adenocarcinoma, Adenosquamous) • PS 0,1 • Age >18,no upper limit providing deemed fit to receive CRT • Adequate renal,liver,BM function,normal ECG • Informed consent

  8. CX II Study • Weekly Paclitaxel (80mg/m2) & Weeks 1-6 • Carboplatin (AUC2) • Followed by radical ChemoRT Weeks 7-13 (cisplatin 40 mg/m2)

  9. Statistical considerations • 50 patients with LACC- (80% power , one sided test at 5% level to detect a response rate of at least 85%) • Toxicity rate >20% - trial to be stopped

  10. Results • 46 patients recruited from 3 centres • Median age 43 (range 23-71) • Histology -72% SCC -22% Adeno - 6% Adenosq

  11. Results • FIGO stage IB2 - 11% II - 50% ( 3/23 +PALN) III - 33% (3/15 +PALN) Iva - 6%

  12. Results -Toxicity • G3/4 Haematological 11% • G3/4 Non-haem tox – 11% • G3/4 Haematological 45% • G3/4 Non- haem tox 21% NACT CRT

  13. Results- NACT Compliance

  14. Results- Radiotherapy Compliance • 96% (44/46 ) completed RT without delay • 96% (42/44) completed brachytherapy • 78% (36/46) had minimum 4 cycles weekly cisplatin

  15. Outcome • 44 pts assessable for response • CR/PR - Post NACT - 68% [95% CI 52-81%] -12 Weeks post CRT - 82% [95% CI 67-92%] • Positive PALN 6 pts- 5 completed all treatment 4/5 NED

  16. Conclusions -1 • Dose dense NACT with weekly C&P followed by radical CRT is feasible with acceptable toxicity • High response rate (68%) to short course of induction chemotherapy • NACT did not result in any disruption to CRT

  17. Conclusions - 2 • 89% completed CRT within 50 days and 78% completed at least 4 cycles of cisplatin • Survival at 2 years is 79% (median FU 23.2 months) • This approach merits further investigation in a randomised phase 3 trial

  18. Proposed Phase 3 trial in LACC

  19. Proposal for Phase 3 trial • Include allthose suitable & fit for CRT • Stratify according to node status • Stratify according to RT dose / institution • Record tumour vol in addition to FIGO stage

  20. Proposal cont’d • Collection of tissue for translational research • Substudy of functional imaging to assess response to IC - ?DCE- MRI • QOL assessment

  21. Outcome measures • Primary endpoint - OS at 5 years • Secondary endpoints- PFS Toxicity QOL Pattern relapse Relationship between functional imaging and outcome

  22. Statistics • Sample size of 1100 provide 80% power to detect a 7% increase in 5 year OS ( 66 to 73%) (HR 0.75 , 2 sided test at 5% level) • Assumes accrual over 4 years with 4 years FU

  23. What next? Upfront chemotherapy • Short course 6 weeks • Minimal toxicity • No disruption to CRT • Overall treatment time 13 weeks Outback chemotherapy • 4 cycles q3weeks • Haem/GI tox likely to be significant • Compliance likely to be poor • Overall treatment time 20 weeks

  24. Acknowledge & Address problems /limitations of conducting a large international study where – • differences in expertise –radiology/ nodal staging • variations in RT dose & fractitionation • quality assurance for RT etc • Potential difficulties in delivering a protracted course of treatment & in FU These need to be addressed as the participation of colleagues in developing world & Eastern Europe is essential

More Related