Radiotherapy With Single-Agent Cisplatin or Combination Chemotherapy in Defined Poor-Prognostic Cervical Cancer

Phase III Trial for Primary Radiotherapy With Single-Agent Cisplatin or Combination Chemotherapy in PET/CT Defined Poor-Prognostic Cervical Cancer Patients

Concurrent radiotherapy with cisplatin-based chemotherapy has become the standard treatment for patients with cervical cancer. However, in patients with advanced cervical cancer, half of them treated with contemporary radiotherapy plus single agent cisplatin still suffered from the local or distant relapse. How to improve the treatment outcome of these patients is a very important issue and requires further clinical investigation.

The major aim of this project is to conduct a prospective, randomized phase III clinical trial to examine if cervical cancer patients treated by radiotherapy with cisplatin and gemcitabine have better survival rates than those treated by radiotherapy with cisplatin alone.

Gemcitabine has been demonstrated to be a good radiosensitizer. In keeping with this, few clinical trials in early phases showed promising results when using concurrent radiotherapy with cisplatin and gemcitabine. According to these positive results, the investigators expect this trial has the potential to improve the survival in patients with advanced cervical cancer, reduce the medical costs due to tumor relapse, and then benefit the whole society.

I). Study end points Primary end point: Patient survival, including overall survival and progression-free survival.

Secondary end points:

1. Acute toxicity during treatment
2. Tumor response rates
3. Sites of recurrence
4. Long-term complications and quality of life II). Design of study

An open-label, prospective randomized trial with two treatment arms:

• Arm I: Patients receive CCRT with weekly cisplatin only.
• Arm II: Patients receive CCRT with cisplatin plus gemcitabine. III). Study population 1) Number of subjects: A total of 172 patients (86 per treatment arm) will be accrued for this study within 4 years.

Conduct of study

Inclusion Criteria:

• Histologically confirmed primary squamous cell carcinoma of the uterine cervix.
• Previously untreated disease.
• Clinical FIGO stage III-IVa or pelvic/para-aortic lymph node positive by PET examination.
• No known metastases to supraclavicular nodes or other organs outside the radiotherapy field.
• Ages eligible: 35 years - 70 years.
• Patients must have adequate bone marrow, pulmonary, liver and renal function documented before radiotherapy. WBC > 3000/mm3, platelet > 100,000/mm3, serum transaminases (GOT, GPT) < 60 IU/ml, total bilirubin < 1.5mg%, creatinine < 1.4mg% (creatinine clearance > 60 ml/min).
• Performance status 0 or 1 (see Appendix I).
• The interval between RT and randomization is not greater than 3 weeks.
• Patients must have signed informed consent to participate this study.

Exclusion Criteria:

• Age > 70 or < 35
• Medical or psychological condition that would preclude treatment.
• Previous chemotherapy or pelvic RT.
• Small cell carcinoma, adenocarcinoma or adenosquamous carcinoma.
• Patient unreliable for treatment completion and follow-up.