Cisplatin and gemcitabine combined with conventional radiation therapy in the treatment of cervical cancer patients results in a favorable outcome but with excess toxicity. The purpose of this study was to evaluate the toxicity profile of dual chemotherapy and highly conformal external beam radiotherapy with image guided adaptive brachytherapy.
Seventeen patients with cervical carcinoma FIGO stage IB2–IIIB were treated with curative intent between 2011 and 2015. A total dose of 50.4 Gy was prescribed to the elective pelvic nodal volume. Patients with 18FDG-PET/CT positive lymph nodes (n = 15; 83.3%) received an additional boost to a total dose of 62 Gy. Chemotherapy prescription goals were: concomitant during 5 weeks of external beam radiotherapy (EBRT) 40 mg/m2 cisplatin and 125 mg/m2 gemcitabine, followed by adjuvant chemotherapy from week 10 (2 cycles 50 mg/m2 cisplatin and 1000 mg/m2 gemcitabine). EBRT was followed by 3–4 fractions (6 Gy per fraction) of intrauterine image guided adaptive brachytherapy. Toxicities were graded according to the common terminology criteria for adverse events (CTCAE v 4.0).
One (6%) patient developed acute grade 3 diarrhea. We did not record any other acute or late gastrointestinal or urogenital toxicity higher that grade 3. Most common acute hematological toxicity was anemia grade 2 recorded in 10 (59%) patients. There was only one case of grade 3 neutropenia (6%). The number of patients that received the complete chemotherapy regimen was gradually declining during the course of therapy. From week 2 to 5, gemcitabine was omitted in 4 (24%),7 (41%), 8 (47%), and 12 (71%) patients respectively, similarly, cisplatin was omitted in 2 (12%),3 (18%),1 (6%) and 7 (41%) patients respectively. Adjuvant chemotherapy was omitted in 8 patients (47%). During a median follow-up time of 20 months (5 to 63 months) 6 (35%) patients developed disease relapse with 5 (29%) of them in the form of systemic disease.
In contrast to previous findings cisplatin and gemcitabine in combination with highly conformal radiation therapy seems to have an acceptable toxicity profile. Further studies are needed to determine the optimal dosage of the proposed therapy concept.
Kidd EA, Siegel BA, Dehdashti F, Rader JS, Mutic S, Mutch DG, Powell MA, Grigsby PW. Clinical outcomes of definitive intensity-modulated radiation therapy with fluorodeoxyglucose-positron emission tomography simulation in patients with locally advanced cervical cancer. Int J Radiat Oncol Biol Phys. 2010;77(4):1085–91. CrossRefPubMed
Gandhi AK, Sharma DN, Rath GK, Julka PK, Subramani V, Sharma S, Manigandan D, Laviraj MA, Kumar S, Thulkar S. Early clinical outcomes and toxicity of intensity modulated versus conventional pelvic radiation therapy for locally advanced cervix carcinoma: a prospective randomized study. Int J Radiat Oncol Biol Phys. 2013;87(3):542–8. CrossRefPubMed
Duenas-Gonzalez A, Zarba JJ, Patel F, Alcedo JC, Beslija S, Casanova L, Pattaranutaporn P, Hameed S, Blair JM, Barraclough H, et al. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011;29(13):1678–85. CrossRefPubMed
Potter R, Dimopoulos J, Kirisits C, Lang S, Haie-Meder C, Briot E, Dumas I, Van Limbergen E, De Brabandere M, Nulens A, et al. Recommendations for image-based intracavitary brachytherapy of cervix cancer: the GYN GEC ESTRO working group point of view: in regard to nag et al. (Int J Radiat Oncol biol phys 2004;60:1160-1172). Int J Radiat Oncol Biol Phys. 2005;62(1):293–5. author reply 295-296 CrossRefPubMed
Chemoradiotherapy for Cervical Cancer Meta-Analysis C. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008;26(35):5802–12. CrossRef
Hertel LW, Boder GB, Kroin JS, Rinzel SM, Poore GA, Todd GC, Grindey GB. Evaluation of the antitumor activity of gemcitabine (2′,2′-difluoro-2′-deoxycytidine). Cancer Res. 1990;50(14):4417–22. PubMed
Lawrence TS, Eisbruch A, Shewach DS. Gemcitabine-mediated radiosensitization. Semin Oncol. 1997;24(2 Suppl 7):S7. -24-S27-28 PubMed
Dueñas-Gonzalez A, Lopez-Graniel C, Gonzalez A, Reyes M, Mota A, Muñoz D, Solorza G, Hinojosa LM, Guadarrama R, Florentino R, et al. A phase II study of gemcitabine and cisplatin combination as induction chemotherapy for untreated locally advanced cervical carcinoma. Ann Oncol. 2001;12(4):541–7. CrossRefPubMed
Duenas-Gonzalez A, Lopez-Graniel C, Gonzalez-Enciso A, Mohar A, Rivera L, Mota A, Guadarrama R, Chanona G, De La Garza J. Concomitant chemoradiation versus neoadjuvant chemotherapy in locally advanced cervical carcinoma: results from two consecutive phase II studies. Ann Oncol. 2002;13(8):1212–9. CrossRefPubMed
Erpolat OP, Alco G, Caglar HB, Igdem S, Saran A, Dagoglu N, Aslay I, Ozsaran Z, Demirci S, Keven E, et al. Comparison of hematologic toxicity between 3DCRT and IMRT planning in cervical cancer patients after concurrent chemoradiotherapy: a national multi-center study. Eur J Gynaecol Oncol. 2014;35(1):62–6. PubMed
- Highly conformal combined radiotherapy with cisplatin and gemcitabine for treatment of loco-regionally advanced cervical cancer – a retrospective study
Eugenia Vlaskou Badra
Chittazhathu Kurian Kuruvilla Yojena
Daniel M. Aebersold
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II