Phase III trial to evaluate the efficacy of maintaining hemoglobin levels above 12.0 g/dL with erythropoietin vs above 10.0 g/dL without erythropoietin in anemic patients receiving concurrent radiation and cisplatin for cervical cancer.
OBJECTIVE
To determine whether maintaining HGB levels > or = 12.0 g/dL with recombinant human erythropoietin (R-HUEPO) compared to "standard" treatment (transfusion for HGB < or = 10.0 g/dL) improves progression-free survival (PFS), overall survival (OS) and local control (LC) in women receiving concurrent weekly cisplatin and radiation (CT/RT) for carcinoma of the cervix. In addition, to determine whether platinum-DNA adducts were associated with clinical characteristics or outcome.


METHODS
Patients with stage IIB-IVA cervical cancer and HGB < 14.0 g/dL were randomly assigned to CT/RT+/-R-HUEPO (40,000 units s.c. weekly). R-HUEPO was stopped if HGB > 14.0 g/dL. Endpoints were PFS, OS and LC. Platinum-DNA adducts were quantified using immunocytochemistry assay in buccal cells.


RESULTS
Between 08/01 and 09/03, 109 of 114 patients accrued were eligible. Fifty-two received CT/RT and 57 CT/RT+R-HUEPO. The study closed prematurely, with less than 25% of the planned accrual, due to potential concerns for thromboembolic event (TE) with R-HUEPO. Median follow-up was 37 months (range 9.8-50.4 months). PFS and OS at 3 years should be 65% and 75% for CT/RT and 58% and 61% for CT/RT+R-HUEPO, respectively. TE occurred in 4/52 receiving CT/RT and 11/57 with CT/RT+R-HUEPO, not all considered treatment related. No deaths occurred from TE. High-platinum adducts were associated with inferior PFS and LC.


CONCLUSIONS
TE is common in cervical cancer patients receiving CT/RT. Difference in TE rate between the two treatments was not statistically significant. The impact of maintaining HGB level > 12.0 g/dL on PFS, OS and LC remains undetermined.
Thomas
Gillian
G
Toronto Sunnybrook Cancer Center, University of Toronto, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5. Gillian.thomas@sunnybrook.ca
Ali
Shamshad
S
Hoebers
Frank J P
FJ
Darcy
Kathleen M
KM
Rodgers
William H
WH
Patel
Malti
M
Abulafia
Ovardia
O
Lucci
Joseph A
JA
Begg
Adrian C
AC
D000328:Adult; D000368:Aged; D000740:Anemia / Q000097:blood / Q000188:drug therapy*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018736:DNA Adducts; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011994:Recombinant Proteins; D013923:Thromboembolism / Q000139:chemically induced; D002583:Uterine Cervical Neoplasms / Q000097:blood* / Q000473:pathology / Q000628:therapy*
D000970:Antineoplastic Agents; D018736:DNA Adducts; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D002945:Cisplatin