Adjusted Nab-Paclitaxel/Gemcitabine Regimen Less Toxic in Pancreatic Cancer

Tanios Bekaii-Saab, MD

Changing the administration schedule for gemcitabine plus nab-paclitaxel (Abraxane) from weekly to every other week significantly reduced side effects without impacting efficacy as a frontline treatment for patients with metastatic pancreatic cancer, according to a retrospective study presented at the 2015 GI Cancers Symposium.

The less intense treatment schedule demonstrated a median overall survival (OS) of 11.1 months and a median progression-free survival (PFS) of 4.8 months. Moreover, the change in dosing reduced patient medical costs by $5,500 per month.

“Shifting this treatment to every other week gives the immune system time to recover between chemotherapy sessions and results in less overall toxicity. It also means fewer visits to the infusion center to receive chemotherapy,” study author Tanios Bekaii-Saab, MD, gastrointestinal oncology section chief at The Ohio State University Comprehensive Cancer Center (OSUCCC) — James, said in a statement. “This less-intense, every other week treatment approach seems to be effective in treating our patients with metastatic pancreatic cancer while significantly reducing side effects that impact quality of life.”

The FDA approved the combination regimen of gemcitabine and nab-paclitaxel for the treatment of patients with metastatic pancreatic cancer in September 2013. The approval was based on results from the MPACT trial, which showed that weekly nab-paclitaxel combined with gemcitabine significantly improved both OS and PFS.

In the study, the median OS was 8.5 months with nab-paclitaxel plus gemcitabine versus 6.7 months with gemcitabine alone (HR = 0.72; P < .0001). The median PFS was 5.5 months with the combination versus 3.7 months with gemcitabine alone (HR = 0.69; P < .0001).

“The combination of gemcitabine and nab-paclitaxel in pancreatic cancer is one of the most recent advances in pancreatic cancer treatment and has been shown to improve survival when compared to gemcitabine alone,” first author Kavya Krishna, MD, a hematology oncology fellow at The OSUCCC — James, said in a statement. “But this improved survival comes with increased toxic side effects that can affect quality of life. We sought an alternative regimen that would prolong treatment effectiveness and reduce side effects.”

The singe-institution retrospective study examining the new schedule was based on information in a prospectively maintained database. The analysis looked at 69 patients with pancreatic cancer who received the gemcitabine and nab-paclitaxel regimen on days 1 and 15 of a 28-day treatment cycle. Of these patients, 49 had previously untreated metastatic pancreatic cancer and the remaining 20 patients had progressed on other treatments or had locally advanced or borderline resectable disease. The median age of patients in the study was 65.

Compared with the MPACT study, the rate of adverse events was considerably less. The incidence of neurological toxicity was less than 2% with the adjusted regimen compared with 17% in the MPACT study. Severe low blood cell counts were seen in 10% of patients with the every other week dose versus 38% with the weekly schedule. Growth factor injections were required in 8% of patients in the database analysis compared with 26% in the MPACT study.

Grade 3 or greater neutropenia (19% vs 38%), anemia (11% vs 13%), thrombocytopenia (3% vs 13%), fatigue (1.6% vs 17%), and diarrhea (1.6% vs 6%) were markedly less with the less intense regimen. Additionally, the rate of neuropathy was 1.6% with the every other week dose versus 7% with weekly nab-paclitaxel plus gemcitabine.

These new findings could significantly improve the quality of life for pancreatic cancer patients, said Krishna. “Pancreatic cancer is an especially difficult diagnosis, so weighing the survival benefit of available treatments against how treatment side effects will impact a patient’s remaining life is a critically important part of the treatment planning process.”

Krishna K, Blazer MA, Wei L, et al. Modified gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer (MPC): A single-institution experience. 2015 Gastrointestinal Cancers Symposium; January 15-17, 2015; San Francisco, CA. Abstract 366.

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