Efficacy of Low-Dose Gemcitabine, Paclitaxel, Sorafenib for Cisplatin-Resistant Urothelial Cancers

Despite a high rate of hematologic toxicity, combined low-dose gemcitabine (Gemzar), paclitaxel, and sorafenib (Nexavar) (LD-GPS) showed promise as a well-tolerated salvage therapy in a small group of patients with cisplatin-resistant urothelial cancer (CDDP-resistant UC), reported researchers from the Nagasaki University Graduate School of Biomedical Sciences in Japan. The findings were reported in a poster presentation at the 2016 Genitourinary Cancers Symposium, held January 7-9, 2016, in San Francisco.   

“LD-GPS therapy is feasible and well-tolerated as third-line regimen,” reported lead author Yasuyoshi Miyata, MD, PhD, and coauthors.

“Quality of life was maintained and improvements in their pain levels were found after treatment,” the researchers noted. “This study is the first report of a prospective trial to investigate the safety, maintenance of quality of life, changes in pain relief, and anti-cancer effects of LD-GPS regimen in patients with CDDP-resistant UC.”

Patients treated with first-line cisplatin-based regimens in most cases experience relapse. “No standard salvage therapies have been devised for use after such chemotherapy,” the researchers reported. Several attempts to develop such therapies have been halted because of severe adverse events, they noted.

“In recent years, we reported low-dose combined therapy of gemcitabine and paclitaxel [LD-GP] are safe and useful for such patients,” the team noted. “In this study, we evaluated safety and effects including pain relief of combined therapy of LD-GP and low-dose sorafenib (LD-GPS) as second- or third-line chemotherapy in patients with cisplatin-resistant urothelial cancers.”

Twenty patients refractor to cisplatin regimens were administered LD-GPS (gemcitabine 700 mg/m² plus paclitaxel 70 mg/m² on day 1 and sorafenib 400 mg/day from day 8 to 21, on 28-day cycles). Short-form survey (SF)-36 and the visual analogue scale (VAS) were used to assess quality of life and pain relief, at baseline and at 8 weeks after LD-GPS initiation. CT or MRI imaging was performed after 2 cycles of treatment.

Two of the 20 participants stopped participating in the study during first-cycle sorafenib administration because of skin rash or appetite loss.

“The most common adverse event [AE] was hematologic toxicity,” affecting 90% of participants, the researchers reported. Severe-AE anemia was reported for one patient.

“Among 18 patients, partial response and stable disease were shown in 2 (11%) and 11 (61%) patients, respectively,” they reported. “Median survival periods from starting LD-GPS therapy was 6 (range, 2 to 16) months” and three study participants survived longer than 1 year.

“Fifteen patients (83%) were judged as [experiencing] positive effects for pain relief,” as assessed by VAS scores and decreased analgesic consumption, they reported (VAS P = .012 for patients administered second-line LD-GPS and P = .028 for third-line patients).

“From these results, we will do further research regarding anti-tumoral effects including prolongation of survival,” the team reported.