Meeting News

Alternative chemotherapy dosing schedule appears safe in patients with bladder cancer

CHICAGO — A “split” schedule of cisplatin-based chemotherapy conferred lower pathologic response rates compared with a convention schedule in patients with muscle-invasive bladder cancer, according to study results presented at ASCO Annual Meeting.

“Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the current standard-of-care for patients with muscle-invasive bladder cancer,” Chelsea K. Osterman, MD, of the Hospital of the University of Pennsylvania, told HemOnc Today. “However, many patients cannot receive cisplatin due to renal impairment. For some patients with borderline renal function, the total dose of cisplatin is commonly ‘split’ over 2 days to reduce risk of nephrotoxicity, but the efficacy of this alternative dosing strategy is still unclear.”

Osterman and colleagues conducted a retrospective, multi-institutional, matched cohort study of 80 patients with muscle-invasive bladder cancer who received either split schedule cisplatin – 35 mg/m2 on days 1 and 8 – or convention schedule cisplatin – 35 mg/m2 on days 1 and 2.

The aim of the study was to assess the efficacy and safety of the dosing schedules in comparison to each other, Osterman said.

Complete and pathologic response served as the primary endpoint.

Patients who received a conventional dosing schedule of cisplatin-based chemotherapy (n = 40; median age, 65.5 years; 82.5% male) experienced a complete response of 32.5 % vs. 17.5% in patients who received a split dosing schedule (n = 40; median age, 71 years; 65% male) (OR = 0.45; 95% CI, 0.16-1.31).

“We were surprised to find that the complete pathologic response rate for patients receiving split schedule was numerically lower than conventional schedule,” Osterman said. “These results should be viewed in context of historical pathologic response rates of patients who underwent transurethral resection alone followed by cystectomy and recent pathologic response rates associated with neoadjuvant immunotherapy.”

A conventional dosing schedule induced a partial response in 45% of patients vs. 27.5% in patients who received a split dosing schedule (OR = 0.53; 95% CI, 0.23-1.26).

“We found that patients who received split schedule cisplatin had lower rates of complete pathologic response and tumor down-staging at time of cystectomy, although this difference did not reach statistical significance,” she said. “Importantly, there were similar rates of toxicity, including renal impairment, between the two groups.”

The most common adverse events to occur in each group included renal impairment (SS = 45%; CS = 35%), ototoxicity (SS = 5%; CS = 12.5%) and a thromboembolic event (SS = 12.5%; CS = 15%).

“Our results suggest that although split schedule cisplatin is likely a reasonable alternative to conventional dose cisplatin, given the numerically lower rates of response associated with split schedule cisplatin, careful consideration should be taken prior to the use of split schedule cisplatin,” she said. “This approach should be reserved for patients with confirmed creatinine clearance of 40-60 mL/min.”

Osterman acknowledged that there were some limitations to the study and that more research is needed.

“A larger, adequately powered, prospective study is needed to detect whether there is a true difference in response rate or survival between these two dosing strategies,” she said. – by Ryan McDonald

Reference:

Osterman CK, et al. Abstract 4545. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Disclosures: Osterman reports no relevant financial disclosures.

CHICAGO — A “split” schedule of cisplatin-based chemotherapy conferred lower pathologic response rates compared with a convention schedule in patients with muscle-invasive bladder cancer, according to study results presented at ASCO Annual Meeting.

“Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the current standard-of-care for patients with muscle-invasive bladder cancer,” Chelsea K. Osterman, MD, of the Hospital of the University of Pennsylvania, told HemOnc Today. “However, many patients cannot receive cisplatin due to renal impairment. For some patients with borderline renal function, the total dose of cisplatin is commonly ‘split’ over 2 days to reduce risk of nephrotoxicity, but the efficacy of this alternative dosing strategy is still unclear.”

Osterman and colleagues conducted a retrospective, multi-institutional, matched cohort study of 80 patients with muscle-invasive bladder cancer who received either split schedule cisplatin – 35 mg/m2 on days 1 and 8 – or convention schedule cisplatin – 35 mg/m2 on days 1 and 2.

The aim of the study was to assess the efficacy and safety of the dosing schedules in comparison to each other, Osterman said.

Complete and pathologic response served as the primary endpoint.

Patients who received a conventional dosing schedule of cisplatin-based chemotherapy (n = 40; median age, 65.5 years; 82.5% male) experienced a complete response of 32.5 % vs. 17.5% in patients who received a split dosing schedule (n = 40; median age, 71 years; 65% male) (OR = 0.45; 95% CI, 0.16-1.31).

“We were surprised to find that the complete pathologic response rate for patients receiving split schedule was numerically lower than conventional schedule,” Osterman said. “These results should be viewed in context of historical pathologic response rates of patients who underwent transurethral resection alone followed by cystectomy and recent pathologic response rates associated with neoadjuvant immunotherapy.”

A conventional dosing schedule induced a partial response in 45% of patients vs. 27.5% in patients who received a split dosing schedule (OR = 0.53; 95% CI, 0.23-1.26).

“We found that patients who received split schedule cisplatin had lower rates of complete pathologic response and tumor down-staging at time of cystectomy, although this difference did not reach statistical significance,” she said. “Importantly, there were similar rates of toxicity, including renal impairment, between the two groups.”

The most common adverse events to occur in each group included renal impairment (SS = 45%; CS = 35%), ototoxicity (SS = 5%; CS = 12.5%) and a thromboembolic event (SS = 12.5%; CS = 15%).

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“Our results suggest that although split schedule cisplatin is likely a reasonable alternative to conventional dose cisplatin, given the numerically lower rates of response associated with split schedule cisplatin, careful consideration should be taken prior to the use of split schedule cisplatin,” she said. “This approach should be reserved for patients with confirmed creatinine clearance of 40-60 mL/min.”

Osterman acknowledged that there were some limitations to the study and that more research is needed.

“A larger, adequately powered, prospective study is needed to detect whether there is a true difference in response rate or survival between these two dosing strategies,” she said. – by Ryan McDonald

Reference:

Osterman CK, et al. Abstract 4545. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.

Disclosures: Osterman reports no relevant financial disclosures.

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