Study With Intensity Modulated Radiation Therapy With Cisplatin to Treat Stage I-IVA Cervical Cancer

• Number of Patients with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 10 weeks while on Treatment ] [ Designated as safety issue: Yes ]
  To test whether IMRT will reduce the rate of acute grade ≥ 3 hematologic or clinically significant grade ≥ 2 gastrointestinal toxicity compared to conventional RT techniques for cervical cancer patients treated with concurrent cisplatin
  
  

• Number of Patients with Acute and Late Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 36 months post treatment ] [ Designated as safety issue: Yes ]
  To estimate and compare the probability of acute and late adverse events
  
  
• Number of Patients with Locoregional Failure as a Measure of Recurrence [ Time Frame: Up to 36 Months post treatment ] [ Designated as safety issue: No ]
  To estimate and compare efficacy of cisplatin/IMRT in terms of locoregional failure, disease-specific survival, disease-free survival, and overall survival.
  
  

Radiation: Intensity Modulated Radiation Therapy (IMRT)
45.0 Gy (intact) or 50.4 Gy (postoperative high-risk) in 1.8 Gy daily fractions over 5-5.5 weeks
Drug: Cisplatin
Weekly infusion of 40 mg/m2 (80 mg max) x 5 weeks

Multiple randomized controlled trials have established concurrent cisplatin-based chemoradiotherapy as the standard of care for locally advanced cervical cancer [3-8]. The addition of concurrent cisplatin to radiotherapy (RT) increases pelvic control, disease-free survival (DFS) and overall survival; however, 5-year DFS and overall survival are still only approximately 60% and 5-year pelvic failure is approximately 30%. Moreover, acute gastrointestinal (GI) and hematologic toxicity are increased. Approximately 30% of patients will experience acute grade ≥ 3 toxicity, predominantly GI and hematologic. Methods to reduce toxicity during chemoradiotherapy, particularly gastrointestinal and hematologic, could mitigate this toxicity and take advantage of the therapeutic benefits of intensive concurrent chemotherapy.

Intensity modulated radiation therapy (IMRT) is a modern RT technique that differs from conventional techniques in many ways. First, patients undergo computed tomography (CT) simulation so that customized target volumes can be defined 3-dimensionally. IMRT treatment planning involves multiple beam angles and uses computerized inverse treatment planning optimization algorithms to identify dose distributions and intensity patterns that conform dose to the target, reducing radiation dose to surrounding tissues. IMRT delivery is typically accomplished with the use of multileaf collimators, which involve small motorized leaflets (collimators) that move in and out of the beam path, modulating the dose intensity.