Cervical cancer in 2002 (n=500,000) (Developed and developing countries)

1. Trial ConceptWeekly VS Three Weekly Chemotherapy for Chemoradiation in Cervical CancerDr Sarikapan Wilailak** Endorsed by the TGCS (Thai Gynecologic Cancer Society)

2. Cervical cancer in 2002 (n=500,000)(Developed and developing countries) Ferlay J et al. Globocan 2002. IARC 2004.

3. Cancer in Thailand, Vol.IV, 1998-2000: 2007

4. New cases / year: 6,243 Deaths / year: 2,620 In Thailand, each day 7 women die from cervical cancer Ferlay J et al. Globocan 2002. IARC 2004

5. Concurrent chemoradiation

6. In 1999, the USNCI issued a statement that concurrent chemoradiation should be considered for all patients with advanced cervical cancer (based on 5 RCT: and recently Keys et al, Marris et al., Rose et al., Whitney et al., Peters et al.)

7. Meta analysis of Concurrent Chemo RT vs RT (18 RCT) Chemoradiotherapy for cervical cancer meta-analysis collaboration. ‘J Clin Oncol 2008:26:5802-12

9. Nowadays, concurrent chemoradiation has become the gold standard treatment for locally advanced cervical cancer.

10. Weekly cisplatin • VS Three weekly cisplatin

11. Weekly VS three weekly • Three weekly chemotherapy could save a considerable amount of resources • There has been no randomized study that compares the two types of chemotherapeutic administration mentioned.

12. Weekly VS three weekly • The question of interest in this proposal is whether weekly or three weekly chemotherapy for chemoradiation in locally-advanced cervical cancer is comparable in terms of efficacy, toxicities, and cost effectiveness.

13. Objectives Primary objectives will be to determine: • Progression-free survival • Acute toxicities • Cost effectiveness of the treatments Secondary objectives will be to determine: • Overall survival • long-term toxicities • Patterns of disease recurrence • Acceptability of patients • Patients’ quality of life

14. Inclusion criteria • Stage IB2 to IVA • Squamous and adenocarcinoma • ECOG performance status 0-2 • WBC ≥ 3.0 x 109/L and ANC ≥ 1.5 x 109/L • Platelets ≥ 100 x 109/L • Bilirubin ≤ 1.5 x UNL • AST/ALT ≤ 2.5 x UNL • Adequate renal function: creatinine ≤ 1.5 ? or calculated creatinine clearance (CockCroft-Gault Formula) ≥60ml/min • No contraindication to the use of cisplatin • Informed consent

15. Exclusion criteria • High-risk histologies (adenosquamous, clear cell etc) • Neoadjuvant chemotherapy • Previous pelvic radiotherapy • Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, who had (or have) any evidence of the other cancer present within the last 5 years • Pregnancy • Serious illness or medical condition that precludes the safe administration of the trial treatment • HIV positive

16. Study Design and procedure • multi-centre randomized phase III trial. • Arm A: Weekly chemoradiation • Arm B: Three weekly chemoradiation • Standard radiation treatment will be given in both arms • The overall treatment time should not exceed eight weeks.

17. In arm A, cisplatin will be given during the radiation at a dose of 40mg/m2 weekly for 6 doses, within 4 weeks of completion of all radiation treatment. • In arm B, cisplatin will be given during the radiation at a dose of 70mg/m2 three weekly for 3 doses, within 4 weeks of completion of all radiation treatment.

18. Outcomes Primary outcomes: • Progression-free survival rates • Acute toxicity rate • Cost effectiveness ratio of the treatments Secondary outcomes: • Overall survival rates • long-term toxicity rate • Patterns of disease recurrence • Acceptability rate of patients • Patients’ quality of life score