Cancer Treatment Today

The gemcitabine/ cisplatin regimen is well studied for pancreatic cancer and as is the drug Abraxane in various combinations. At the January 2017 Gastrointestinal Cancers Symposium (American Society of Clinical Oncology  ASCO) there was a presentation of theg results of an ongoing Phase Ib/II clinical trial that assess the addition of cisplatin to the original gemcitabine plus Abraxane regimen in the treatment of metastatic pancreatic cancer (clinical trial: NCT01893801).

In the 2015 AACR meeting, the researchers published their work in a meeting abstract entitled, “High complete and partial response rate in a phase Ib pilot trial with cisplatin plus albumin-bound paclitaxel and gemcitabine in patients with advanced pancreatic cancer.” Under the rationale that pancreatic cancer not infrequently demonstrates abnormalities in DNA repair that may tend to respond to such entities as platinum salts, they added cisplatin to the gemcitabine plus Abraxane chemotherapy regimen for patients with stage IV pancreatic cancer. Ten patients with advanced pancreatic cancer were enrolled with two showing a complete response, six showing a partial response, one offering stable disease, and one demonstrating progression of their pancreatic cancer. Four patients had serious adverse side effects including sepsis/pneumonia, bacteremia, clostridium difficile colitis, and neutropenic fever/pneumonia. Despite the sobering events profile, the clinical results were encouraging enough for the researchers to move forward to the stage II status of the clinical trial.

In the 2017 Gastrointestinal Cancers Symposium, the research team both published an abstract and presented their further results in a Poster Presentation, “A phase Ib/II pilot trial with nab-paclitaxel plus gemcitabine plus cisplatin in patients with stage IV pancreatic cancer.” The 25 patients in three U.S. sites met inclusion criteria including being diagnosed with stage IV pancreatic cancer between December 2013 and July 2016. All of the patients were treated with the three-drug regimen. 20% had their tumor resected. 18 of the 25 patients had a greater than 30% reduction in the pancreatic cancer tumor size. The median survival to date (at the time of presentation) was 16.5 months, with 20% alive at 24 months. 40% of the patients experienced a grade 4 adverse effect including primarily such conditions as thrombocytopenia, anemia, neutropenia, infection, or substantive diarrhea.

Pase 2 results were published recently. Shroff et al concluded that treatment with nab-paclitaxel plus gemcitabine-cisplatin prolonged median progression-free survival and overall survival vs those reported for historical controls treated with gemcitabine-cisplatin alone. These findings will be tested in a phase 3 randomized clinical trial.

Another pahse Ib/II study by Jameson concluded that this triple drug regimen showed substantial clinical activity in this small study. Although the primary end point was not reached, the high overall response rate, disease control rate, and median survival time among patients with advanced PDA treated with this combination are encouraging.

Proceedings: AACR 106th Annual Meeting; April 18-22, 2015; Philadelphia, PA; Cancer Res 2015;75(15 Suppl):Abstract LB-003. doi:10.1158/1538-7445.

2017 Gastrointestinal Cancers Symposium, ASCO, San Francisco; J Clin Oncol 35, 2017 (suppl 4S; abstract 341); Poster Session B Board #F11.

Shroff RT, Javle MM, Xiao L, Kaseb AO, Varadhachary GR, Wolff RA, Raghav KPS, Iwasaki M, Masci P, Ramanathan RK, Ahn DH, Bekaii-Saab TS, Borad MJ. Gemcitabine, Cisplatin, and nab-Paclitaxel for the Treatment of Advanced Biliary Tract Cancers: A Phase 2 Clinical Trial. JAMA Oncol. 2019 Jun 1;5(6):824-830.

Gayle S. Jameson,et al,Response Rate Following Albumin-Bound Paclitaxel Plus Gemcitabine Plus Cisplatin Treatment Among Patients With Advanced Pancreatic Cancer
A Phase 1b/2 Pilot Clinical Trial. JAMA Oncol.  2020;6(1):125-132.