Sequential Adjuvant Chemo-Radiotherapy With Vs. Without Erythropoeitin For Patients With High-Risk Cervical Cancer-Second Analysis Of A Prospective, Randomized, Open And Controlled AGO- AND Sequential Adjuvant Chemo-Radiotherapy With Vs. Without Erythropoeitin For Patients With High-Risk Cervical Cancer-Second Analysis Of A Prospective, Randomized, Open And Controlled AGO- And NOGGO-Intergroup Study

Reviewer: Roberto Santiago, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 19, 2002

Presenter: Jens U Blohmer
Presenter's Affiliation: Humboldt University, Berlin, Germany
Type of Session: Poster

Background

The aim of the study was to compare the disease-free survival achieved by an adjuvant sequential chemoradiotherapy regimen with vs. without Erythropoeitin (EPO) for patients with high-risk cervical cancer
The second endpoints of the study included toxicity, number of transfusions, quality of life, and survival

Materials and Methods

All patients underwent a radical hysterectomy and adjuvant chemotherapy and radiation therapy was recommended postoperatively
Patients were stratified according to pelvic nodes (pN0 vs. pN1), stage (Ib, IIa vs. IIb), and resection (R0 vs. R1)
Patients were randomized to sequential chemotherapy followed by radiotherapy with EPO or without EPO
All patients received 4 cycles (q21d) of ifosphamide (1.6 mg/m2, d1-3), carboplatin (AUC 4, d1) and subsequent radiotherapy (5 weekly fractions of 1.8-2 Gy up to 50-50.5 Gy)
EPO arm: EPO 10,000 IU three times a week + oral iron supplements up to a Hb target value of 13 g/dl
No EPO arm: only transfusions were allowed
128 patients from 63 clinics were randomized to each arm between 01/1999 and 03/2001

Results

EPO was given as planned in about half of the patients analyzed in the EPO-arm
The EPO-application was stopped in 33% of patients because a Hb > 14g/dl was achieved
The EPO dose was reduced (10.000 IE/3x/week) in 8% of patients because a Hb > 13 g/dl was achieved
The median doses of carboplatin and ifosphamide (in both arms) were AUC 4 and 1.6 g/m2, respectively
84% of the patients completed the 4 cycles of chemotherapy
Median radiation dose was 50.4 Gy
Median follow-up was 64.5 weeks
There was a significantly higher recurrence-free survival rate in the EPO-arm (89% vs. 78%, p=0.04)
There was a significant reduction of grade 2 anemia (20% vs. 51%, p=0.01) and in the number of red blood cell (no transfusion required: 91% vs. 67%; p=0.0046) as well as platelet transfusions (p=0.0025) in the EPO-arm

Author's Conclusions

Adjuvant sequential chemoradiotherapy with EPO support in patients with high-risk cervical cancer was demonstrated to be easily tolerated and associated to few treatment interruptions
After a short follow-up period, support with EPO appeared to afford a lower rate of recurrences

Clinical/Scientific Implications

It is plausible that the benefit seen is due to re-oxygenation of hypoxic tumors but further research is needed to confirm this hypotesis.
If these findings are confirmed with further follow-up routine EPO support could become a standard component of chemoradiotherapy for cervical cancer.

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