Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer.

Abstract

PURPOSE:

For unresectable locally advanced (UR-LA) pancreatic cancer, chemoradiotherapy has been recommended by the NCCN guidelines. We designed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine (GnP) for patients with UR-LA pancreatic cancer. The purpose of this phase I study was to determine a recommended dose (RD) for this novel regimen.

METHODS:

Patients with UR-LA pancreatic cancer were eligible. The frequency of dose-limiting toxicities (DLTs) was evaluated, and the RD was determined. Patients were classified according to the designated dose levels of chemoradiotherapy using the GnP regimen. After additional 6 cycles of the GnP regimen were administered, surgery was considered if the patients had stable disease and tumor marker levels had normalized.

RESULTS:

DLT (grade 4 thrombocytopenia) was observed only in 1 of 12 patients, and the RD was set at level 3. Grade 3-4 leukopenia was observed in 9 (75.0%) patients, and neutropenia in 7 (58.3%). The response rate was 41.7%, and the disease control rate was 100%. Conversion surgery was performed in 6 (50%) patients, and curative resection (R0) was performed in all 6 patients (100%). Stratification according to the Evans classification system demonstrated one patient with grade 1b, one with grade 2, two with grade 3, and two with grade 4 disease.

CONCLUSION:

The RD for weekly administration was 800 mg/m2 for gemcitabine and 100 mg/m2 for nab-paclitaxel with a 50.4 Gy radiation. The GnP regimen at this dosage was promising with 6 of 12 patients proceeding to conversion surgery, and should be evaluated further in a phase II trial.

• Authors: Suguru Yamada, Tsutomu Fujii, Yukihiro Yokoyama, Hiroki Kawashima, Osamu Maeda, Kojiro Suzuki, Tohru Okada, Eizaburo Ono, Junpei Yamaguchi, Nao Takano, Hideki Takami, Masamichi Hayashi, Yukiko Niwa, Yoshiki Hirooka, Yoshiyuki Ito, Shinji Naganawa, Yuichi Ando, Masato Nagino, Hidemi Goto, Yasuhiro Kodera
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 81 Issue 5 Pg. 815-821 (05 2018) ISSN: 1432-0843 [Electronic] Germany
• PMID: 29502139 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Deoxycytidine
• Paclitaxel
• Gemcitabine

Topics

• Adult
• Aged
• Albumins (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Chemoradiotherapy (methods)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives)
• Dose-Response Relationship, Drug
• Female
• Humans
• Male
• Middle Aged
• Neoadjuvant Therapy (methods)
• Paclitaxel (administration & dosage, adverse effects)
• Pancreas (pathology, surgery)
• Pancreatectomy
• Pancreatic Neoplasms (pathology, therapy)
• Treatment Outcome
• Gemcitabine