A 2-week pretreatment with 13-cis-retinoic acid + interferon-α-2a prior to definitive radiation improves tumor tissue oxygenation in cervical cancers

Jürgen Dunst*, Gabriele Hänsgen, Ulf Krause, Glenn Füchsel, Uwe Köhler, Axel Becker

*Corresponding author for this work
14 Citations (Scopus)


Background: We have evaluated the tumor tissue pO2 in cervical cancers in patients treated with 13-cis-retinoic acid and interferon-α-2a prior to and during radiotherapy. Patients and Methods: From June 1995 through April 1997, 22 patients with squamous cell carcinoma FIGO IIB/III of the cervix who were scheduled for definitive radiotherapy with curative intent received additional treatment with 13-cis-retinoic acid (cRA, isotretinoin) plus interferon-α-2a (IFN-α-2a) as part of a phase-II protocol. cRA/IFN-α-2a started 14 days prior to radiotherapy (1 mg per kilogramme body weight cRA orally daily plus 6 x 106 IU IFN-α-2a subcutaneously daily). After this induction period, standard radiotherapy was administered (external irradiation with 50.4 Gy in 28 fractions of 1.8 Gy plus HDR-brachytherapy). During radiotherapy, cRA/IFN-α-2a-treatment was continued with 50% of the daily doses. Tumor tissue pO2-measurements were performed prior to and after the cRA/IFN-induction period as well as at 20 Gy and at the end of radiotherapy with an Eppendorf-pO2-histograph. Results: In 11 out of the 22 patients, pO2-measurements were performed prior to the cRA/IFN-induction therapy. The median pO2 of these untreated tumors was 17.7 ± 16.3 mm Hg. The relative frequency of hypoxic readings with pO2-values below 5 mm Hg ranged from 0% to 60.6% (mean 24.3 ± 21.0%). After the 2-week induction period with cRA/IFN, the median pO2 had increased from 17.7 ± 16.3 mm Hg to 27.6 ± 19.1 mm Hg (not significant). In all 5 patients with hypoxic tumors prior to cRA/IFN (median pO2 of 10 mm Hg or less), the median pO2 was above 20 mm Hg after the 2-week cRA/IFN-induction. In this subgroup of hypoxic tumors, the median pO2 increased from 6.3 ± 2.7 mm Hg to 27.0 ± 5.6 mm Hg (p = 0.004, t-test for paired samples). The frequency of hypoxic readings (pO2-values < 5 mm Hg) decreased from 44.7 ± 17.1% to 2.0 ± 2.5% (p = 0.012, t-test for paired samples). There was, however, no obvious volume reduction after 14 weeks of cRA/IFN on clinical examination. A complete clinical remission of the local tumor was observed in 19/22 patients after radiotherapy and additional cRA/IFN-α-2a-treatment. In primarily hypoxic tumors (with a median pO2 below 10 mm Hg prior to treatment), 4/5 achieved complete remission. Conclusions: Pretreatment with cRA/IFN improves oxygenation of primarily hypoxic cervical cancers. The mechanisms of action remain unclear and further investigation of the combination regimen is recommended.

Original languageEnglish
JournalStrahlentherapie und Onkologie
Issue number11
Pages (from-to)571-514
Number of pages58
Publication statusPublished - 11.1998


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