Clinical Drug Experience Knowledgebase

Phase III Randomized Trial of Comparing CCRT vs. RT Alone for Cervical Cancer Patients Primarily Treated by Radiotherapy and With Clinically Defined Good-prognosis

OBJECTIVES:

Primary Objectives:

•To examine if low-risk, as defined by clinical and radiological parameters, stage IB-IIB cervical cancer patients treated by cisplatin-based CCRT have greater toxicities but similar survival rate as those treated by RT alone.

Secondary Objectives:

•To conduct a translational research to find out the molecular markers associated with radiosensitivity and distant metastasis in cervical cancer patients.

104 cases for each arm.(total 208 cases)

Radiotherapy will start within 3 weeks of randomization.

Chemotherapy:

Cisplatin 40mg/M2 IV infusion weekly concurrently with radiotherapy, up to 6 courses.

Investigation during treatment (for patients on both arms)

. Hematology: A complete blood count is required at weekly intervals.
. Renal function: Serum creatinine is required before each course of CT.
. Body weight and performance status: will be evaluated on the day of weekly visit on radiotherapy clinics. Performance status is graded by ECOG scale.
. Quality of life assessment: assess by EORTC-C30 & CX28 scales at pre-RT, 3-4 weeks and 6-7 weeks during RT.

Investigation during follow-up:

When radiotherapy (RT) treatment is completed, patients will be followed up as out-patients basis. The first visit will be within 2 months after last RT. For patients whose tumor does not regress completely at the end of RT, monthly follow-up for at least 3 months or to the time of complete regression is recommended. After first follow-up or time of compete regression of tumor, patients will be followed up at 3-monthly intervals for 2 years, 4-monthly for one year, then 6-monthly.

Quality of life assessment: assess by EORTC-C30 & CX28 scales at 2 months, 4-5 months after RT, then q 6 months x 2 and yearly for another 2 years.

Dosage modification and toxicity Toxicity must be recorded at each attendance for chemotherapy and monthly during radiotherapy on the "on study form".

. Hematological toxicity: ANC < 1500 /mm3 and/or platelet < 100,000 /mm3 prior to chemotherapy will require one week delay in treatment until these levels have been reached. If the parameters are still below requirements 1 week later, administration of chemotherapy could still be proceeded if 1000 50,000 /mm3 at reduced dose (25% off).

Radiotherapy will not be delayed unless severe infection or a white count less than 1000/mm3

. Renal toxicity:

a). Cisplatin: Serum creatinine < 1.5 mg% (creatinine clearance > 70 ml/min): full dose; 1.6-1.9 mg% (or 0.6-0.8 mg% above base line, or Ccr 50-70 ml/min): 25% off; > 2.0 mg% (or > 1.2 mg% over baseline or 50% decrease of Ccr): no cisplatin

. Neurotoxicity: Cisplatin discontinued on Grade 3 neuropathy. 30% dose decrease for Grade 2 neurotoxicity or ototoxicity
. Ototoxicity: Ototoxicity is rare within 4 -6 courses or cisplatin, but if clinical significant deterioration of hearing loss (grade 3) was noted, cisplatin will be discontinued. The aged are more susceptible to ototoxicity.
. Genitourinary complications Urinary tract infection or radiation cystitis may be noted during the course of treatment, CT or CT+RT will be withheld in case of grade 3 toxicity
Gastroenterological toxicity:

Acute radiation enteritis may prelude continuation or delay either CT or CT+RT