Enhanced radiosensitization with interferon-alpha-2b and cisplatin in the treatment of locally advanced cervical carcinoma.
OBJECTIVE
To evaluate the efficacy and toxicity of interferon-alpha-2b (IFN-alpha) and cisplatin given concomitantly with radiation therapy (RT) in the treatment of locally advanced cervical carcinoma.


METHODS
Twenty-one patients with stage bulky Ib-IIIb (Ib, 2; IIa, 2; IIb, 8; IIIb, 9) cervical carcinoma were treated with combined IFN-alpha (5 million IU) subcutaneously three times per week and cisplatin (25 mg/m2) i.v. infusion over 2 h weekly for 7 weeks, given concomitantly with RT (4500 cGy of external beam plus 2 brachytherapy procedures). Total radiation doses delivered ranged from 7500 to 9960 cGy (median, 9300 cGy). Follow-up ranged from 16 to 33 months (median, 25 months).


RESULTS
The 2-year local control rate was 100%. The only sites of disease recurrence were distant. Freedom from distant metastases, disease-free survival, and overall survival at 2 years was 76%. Late complication rates were high. Grade 4 rectosigmoid, bladder, and small bowel complication rates were 49, 18, and 23% at 2 years. Late toxicity was seen earlier than expected with rectosigmoid complications observed 5 to 11.5 months (median, 8 months) after completion of treatment.


CONCLUSIONS
Combination IFN-alpha and cisplatin produced a marked effect of enhanced radiosensitization as evidenced by 100% local tumor control and high late normal tissue complication rates. Due to the unacceptable late toxicity, its routine clinical use cannot be recommended. Further investigation is needed to determine whether a therapeutic window exists such that the use of lower doses of IFN-alpha, cisplatin, or RT can increase tumor control with more acceptable normal tissue toxicity.
Stock
R G
RG
Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York 10029, USA.
Dottino
P
P
Jennings
T S
TS
Terk
M
M
DeWyngaert
J K
JK
Beddoe
A M
AM
Cohen
C
C
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001918:Brachytherapy / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D009367:Neoplasm Staging; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D011994:Recombinant Proteins; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011838:Radiation-Sensitizing Agents; D011994:Recombinant Proteins; D002945:Cisplatin