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A clinical trial comparing concurrent Cisplatin and radiation therapy versus radiation alone for locally advanced Squamous Cell Carcinoma of the cervix carried out by the National Cancer Institute of Canada Clinical Trials Group
Theodore Robnett, MD
OncoLink Assistant Editor
Ultima Vez Modificado: 20 de mayo del 2000
Presenter: Gavin Stuart
Affiliation: NCI Canada, University of Alberta, Edmonton, Canada, others
In 1999, multiple abstracts of phase III trials comparing chemoradiation with radiation alone in localized cervix cancer were presented at ASCO. All of these trials showed that multiagent platinum-containing chemotherapy was associated with improved outcome. The current study is similar in design, but employs platinum alone on the chemotherapy arm.
Materials and Methods:
- This was a phase III randomized trial. Eligibility criteria were : Patients with biopsy confirmed squamous cell carcinoma of the cervix with poor prognostic features (stage IB/IIA/IIB, size > 5 cms) or biopsy confirmed pelvic lymph node involvement or stage IIB with lateral parametrial involvement, or stage III, or IVA of any size.
- Arm 1 patients received pelvic radiation therapy with weekly cisplatin (40 mg/m2). Arm 2 patients received identical pelvic radiation therapy alone.
- Radiation dose: 45 Gray external beam radiation therapy (EBRT) was administered with high, medium, or low dose rate brachytherapy as an option to follow.
- 259 patients were enrolled, 253 patients (arm 1 = 127, arm 2 = 126) were eligible. Median follow up was 65 months (range 6.6 - 102.8 months). 7% of patients in each arm had stage IIIB/IVA disease.
- 79% of arm 1 patients received the specified dose of cisplatin, 86% received 90% of the specified dose. Brachytherap was not given in 9% and 8% of patients in arms 1 and 2, respectively. Duration of delivery time of EBRT was comparable in the arms.
- Acute complications were greater in arm 1, but with a trend toward fewer late complications in arm 1 (6% versus 12%, p = 0.08)
- One year pelvic control rates in arms 1 and 2 were 83% vs 78% (p=0.37), and 5 year survival rates were 59% vs 56% (p = 0.43), respectively.
- Patients in arm 1 had a greater drop in hemoglobin level than in arm 2 (p = 0.003).
- Cox modelling showed failure to complete brachytherapy was an indicator for progressive disease (according to authors, patients did not get brachytherapy when disease was too bulky).
- The question was raised during the session whether Hemoglobin differences accounted for the lack of a difference in outcome. Similarly, a suggestion was made of a future trial with an RT + erythropoeitin arm.
- During the discussion section, a comparison was made of this study versus the previous 5 presented at ASCO 1999. The point was made that the progression free survival (PFS) in the combined modality arm of this trial was comparitable to that of others. It was the radiation therapy alone arm which was significantly better than the RT alone arms of the other trials. Note was made of the relatively low time of delivery of radiation therapy versus that of the other trials. The phenomenon of decreased control with increasing treatment time of radiation therapy is well described in multiple sites, including cervix.
Differences Between Abstract and Presentation:
Hemoglobin data were added during the oral presentation
- Although platinum-containing multiagent chemotherapy regimens appear to significantly effect outcomes in localized cervix cancer, single agent cisplatin (at this dose) in this cohort did not appear to influence local control or overall survival.
- In this population, patients who were not candidates for multiagent chemotherapy due to performance status or comorbidities may be candidates for radiation therapy alone.