Trial Concept Weekly VS Three Weekly Chemotherapy for Chemoradiation in Cervical Cancer

Dr Sarikapan Wilailak** Endorsed by the TGCS (Thai Gynecologic Cancer Society)

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

DEVELOPED COUNTRIES DEVELOPING COUNTRIES

SITEAttrib to HPV (%)

TOTAL cancers

Attrib to HPV

% all cancer

TOTAL cancers

Attrib to

HPV

% all cancer

CERVIX 100 83,400 83,400 1.7% 409,400 409,400 7.0%

Ferlay J et al. Globocan 2002. IARC 2004.

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

New cases / year: 6,243 New cases / year: 6,243

Deaths / year: 2,620 Deaths / year: 2,620

In Thailand, each day 7 women die from cervical

cancer

In Thailand, each day 7 women die from cervical

cancer

Ferlay J et al. Globocan 2002. IARC 2004

Concurrent chemoradiation

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.)

Meta analysis

of Concurrent Chemo RT

vs RT(18 RCT)

Chemoradiotherapy for cervical cancer meta-analysis collaboration. ‘J Clin Oncol 2008:26:5802-12

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

Weekly cisplatin

VS

Three weekly cisplatin

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.

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.

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

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

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

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.

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.

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