Concomitant Chemoradiation in Advanced Stage Carcinoma Cervix
Condition: Cancer of Cervix
MeSH terms: Carcinoma; Uterine Cervical Neoplasms
Study type: Interventional

Summary: 
      A study to evaluate the efficacy of concomitant chemoradiation as compared to radiotherapy
      alone. Concomitant chemoradiation is not a new treatment modality for carcinoma cervix.
      Studies have shown improvement in survivals with chemoradiation, but majority of the patients
      was in early stages. Since this treatment modality has not been tested adequately in advanced
      stages in our setting, the present study is being undertaken. The study arm of chemoradiation
      has the potential to improve the survivals by 10%, but is associated with additional 5% risk
      of toxicities, which are treatable. In the study arm, apart form the standard radiotherapy
      treatment, you will receive weekly chemotherapy injections (Cisplatin) during external
      radiation therapy. The study arm is associated with additional 5% acute hematological and
      gastrointestinal toxicities, which are treatable with medications, blood transfusions,
      modifications in the ongoing treatment etc.
    

Detailed description: 
      Carcinoma cervix is the commonest malignancy seen in Asian women and constitutes
      approximately 30% of all cancers (1). It is also the leading cause of cancer mortality in
      India. Nearly 50% of the patients present with advanced stages (FIGO Stage III/IV). The main
      stay of treatment has traditionally been radical radiation therapy and over decades the
      survival rates have achieved a plateau of 30 - 45% at 5 years. In developing countries the
      socioeconomic problems, illiteracy, late presentation and irregular follow-up have further
      compromised our survivals. Over the last decade there have been studies on the use of
      chemo-radiotherapy in carcinoma cervix. Over 19 randomized trials have been published
      addressing the issue of chemo-radiotherapy. However, heterogeneous data, poor randomization,
      inadequate number of patients, sub-optimal radiotherapy, non-uniform use of chemotherapeutic
      drugs, its sequencing and poor documentation have not yet provided the evidence to
      substantially alter the practice. Hence, meta-analysis of these trials was undertaken to
      further evaluate the role of chemo-radiotherapy in carcinoma cervix (2,3).

      The first meta-analysis published by Cochrane Collaborative Group of 4580 randomized patients
      (19 randomized trials) suggested that chemo-radiation did show an absolute survival benefit
      improvement both in progression free and overall survivals by 16% and 12% respectively
      (p<0.0001). The survivals were significantly better with Cisplatin based concomitant
      chemo-radiation (p<0.0001). Incidentally, the distant metastasis rates were also
      significantly lower in chemo-radiation (p<0.0001). However, all these benefits were seen only
      in early stages. In addition, acute grade 3/4 hematological and gastro-intestinal toxicities
      were higher with chemo-radiation (additional 8% and 5% respectively). The data was
      insufficient to report on late toxicity (2).

      The second meta-analysis of 9 randomized trials, recently published by the Canadian Group to
      evaluate only cisplatin based concomitant chemo-radiation confirms the improvement in overall
      survival (4year survival data) in advanced stages, bulky IB tumors (prior to surgery) and
      high risk early disease (post-surgery). Although acute grade 3/4 hematological and
      gastro-intestinal toxicities were higher in chemo-radiation, they were short-lived, with only
      2 deaths and the remaining resolved with medical treatment. There was no significant increase
      in the late toxicity from the data available.

      Both the Cochrane and Canadian meta-analysis have to a large extent tried to address the role
      of concomitant chemo-radiation, but Carcinoma Cervix Stage III accounted for only 30-35% and
      moreover evaluation with optimal radiation schedules and comparison of late toxicities still
      remains unanswered. What is more important is that the cisplatin is relatively inexpensive
      and is available worldwide. This means that cisplatin-based chemo-radiation is affordable in
      the developing countries where carcinoma cervix still forms the major cancer. However, the
      role of chemo-radiation in Carcinoma Cervix Stage IIIB in a developing countries including
      India still remains unexplored. We propose this randomized study to evaluate the role and
      benefit of chemo-radiation in-patients with cervical cancer.
    

Intervention name(s): CT + RT
Intervention type(s): Other
Intervention description(s): Injection Cisplatin 40mg/m2 weekly for 5 weeks during the entire course of external radiation therapy
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Concomitant chemo-radiation versus radiation alone
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Carcinoma Cervix; FIGO Stage IIIB; Radiation therapy; Chemoradiation; Treatment related toxicities; Cervical Cancer; Cervix Cancer