Whole Abdominal radiotherapy versus combination doxorubicin-cisplatin chemotherapy in advanced endometrial carcinoma: A randomized phase III trial of the Gynecologic Oncology Group

Reviewer: Ryan Smith, MD
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Ultima Vez Modificado: 2 de junio del 2003

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Presenter: M.E. Randall
Presenter's Affiliation: GOG
Type of Session: Plenary

Background

  • Endometrial cancer is the most common gynecologic cancer diagnosed
  • Treatment for stage III endometrial cancer has ranged from no treatment to chemotherapy alone to radiation therapy of various types
  • This study hoped to further define the optimal treatment for stage III/IV endometrial cancer

Materials and Methods

  • 422 patients with FIGO stage III/IV endometrial cancer were entered into study
  • All had initial surgery consisting of TAH/BSO and required optimal debulking to <2cm
  • Surgical staging was also done, but not required if the patient was stage III/IV by other creteria
  • If the PA lymph nodes were positive, the patient was required to have a negative scalene lymph node biopsy and a negative CT of the chest
  • Arm 1-Whole abdominal irradiation (WAI) consisting of 30 Gy in 20 fractions of daily 150 cGy dose using AP/PA fields. Kidney blocks were used in the PA fields only. An additional 15 Gy in 6 fractions were used to boost the pelvis, with boost to the PA nodes if the nodes were positive on biopsy or not sampled
  • Arm 2-Doxorubicin and cisplatin (AP) chemotherapy consisting on doxorubicin 60 mg/m2 + cisplatin 50 mg/m2 every 3 weeks x 7, followed by a cycle of cisplatin only

Results

  • Aproximately 25% were serous or clear cell histology
  • 84% completed the WAI arm, while only 65% completed the AP arm
  • Toxicity was greater in the AP arm. This included significant hematologic toxicity as well as 13% vs 20% grade 3-4 GI toxicity and 0 vs 15% cardiac toxicity
  • 2 yr PFS was improved in the AP arm (58% vs. 48%) and at 5 years (42% vs. 38%). Hazard ratio was 0.81 (.63-1.05) in favor of AP arm
  • PFS was better for AP in Stage III (Hazard ratio of 0.82) and Stage IV (Hazard ratio of 0.56) disease
  • Overall survival was better in the AP arm (Hazard ratio of 0.71 for entire population, 0.67 for stage III, and 0.64 for Stage IV)
  • On multivariate analysis, Stage IV disease, gross residual disease, African American race, (+) cytology, and serous or clear cell histology all predicted for a worse outcome

Author's Conclusions

  • Chemotherapy with AP improves PFS and OS when compared with WAI in patients with Stage III/IV endometrial cancer
  • Toxicity is significantly increased in the AP arm
  • Prognostic factors include stage, amount of residual disease, race, cytology, and cell type
  • Recurrences are still significant (40-50% in stage III and 80-90% in stage IV), so there is a great need to support the GOG study using combination chemotherapy and more limited fields of radiation

Clinical/Scientific Implications

    This was a very important study done to attempt to delineate the optimal treatment for advanced endometrial cancer. However, the results of this suffer from two major flaws. First, the treatments used, while the best known treatment at the time, are now outdated, both in chemotherapy regimen and radiation dose. The other major flaw is that there was no stratification performed in this study whatsoever. There is an extremely large difference between a patient who is deemed stage IIIA based on cytologic sampling and a patient who has distant spread, vaginal spread,or bulky lymph nodes. Therefore, it is not known whether this difference in the data represents true improvement in treatment or simply an imbalance between the populations. In addition, chemotherapy seemed to exert its effect by decreasing early metastatic spread only, which is evidenced by the fact that the curves came together at 5 years, and the largest difference in patterns of failure was that radiation patients failed outside of the pelvis and peritoneum. Also, chemotherapy was not without fairly severe toxicity, in a population of patients who are typically elderly with comorbidities. However, the study did identify various prognostic factors that can be used in the future to stratify and individualize treatment. Stage III and IV disease must be approached individually, concentrating therapy to those areas most at risk for failure, depending on the histology and type of locally advanced disease.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.

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