Highly conformal combined radiotherapy with cisplatin and gemcitabine for treatment of loco-regionally advanced cervical cancer – a retrospective study

Nikola Cihoric, Alexandros Tsikkinis, Eugenia Vlaskou Badra, Markus Glatzer, Urban Novak, Amina Scherz, Mohamed Shelan, Ivan Soldatovic, Chittazhathu Kurian Kuruvilla Yojena, Daniel M. Aebersold, Kristina Lössl

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.