A concurrent chemotherapy and radiotherapy (RT) regimen with cisplatin and paclitaxel yielded a good response rate and strong long-term survival outcomes in patients with locally advanced (LACC) or recurrent cervical cancer (LRCC), according to results of a phase II study presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held earlier this month in Chicago.
The standard treatment for LACC is low-dose cisplatin as a radio-sensitizing agent with concurrent RT. “Paclitaxel binds to tubulin and inhibits the disassembly of microtubules, inhibiting cell division,” wrote study authors led by Milena Bruzzone, MD, of San Martino University Hospital in Italy (abstract 5529).
The new phase II study, which ran from 2000 through 2014, combined paclitaxel with cisplatin at a cytotoxic dose with concurrent RT in 65 patients with LACC or LRCC; patients received cisplatin 75 mg/m2 and paclitaxel 175 mg/m2 every 21 days for 4 courses with concurrent RT at a dose of 50 Gy over 25 courses and high-dose brachytherapy (6 Gy, 3 courses). One patient died during treatment (unrelated to tumor or therapy), leaving 64 evaluable for response. Most patients (93.85%) had an ECOG performance status of 0, and most (96.92%) had squamous histology.
After a median follow-up of 58 months, there were 55 complete responses (84.62%) and 8 partial responses (12.31%), for an overall response rate of 96.92%; 1 patient had stable disease.
The 180-month progression-free survival rate was 66.6%, and the overall survival at that time point was 67.3%. Ten people died during the study; two of those died due to secondary malignancies (one uterine carcinosarcoma, one pancreas adenocarcinoma), and another was diagnosed with endometriod uterine carcinoma. The survival curves showed no deaths beyond about 4 years post-treatment.
There was one grade 4 toxicity (leucopenia) reported during the study. Grade 3 adverse events (AEs) included proctitis (24.61% of patients), leucopenia (15.38%), anemia (15.38%), diarrhea (13.85%), and several others. Grade 1 neuropathy and grade 2 proctitis were among the most common AEs in the trial.
“At 14-year follow-up we reported long-term durable responses,” the authors concluded. “The chemo-radiotherapy regimen was safe,” and they recommend a phase III randomized trial to better establish the regimen’s efficacy.