Phase I study of primary treatment with 5-FU, oxaliplatin, irinotecan, levofolinate, and panitumumab combination chemotherapy in patients with advanced/recurrent colorectal cancer involving the wild-type RAS gene: the JACCRO CC-14 study.

Abstract

BACKGROUND:

FOLFOXIRI is now regarded as the chemotherapy regimen that offers the best platform for the treatment of colorectal cancer. However, the safety and efficacy of FOLFOXIRI + panitumumab has not been demonstrated. We conducted a phase I study to determine the recommended dose of FOLFOXIRI + panitumumab as first-line treatment for RAS wild-type metastatic colorectal cancer (mCRC).

METHODS:

Patients received combination therapy consisting of panitumumab (6 mg/kg on day 1) + FOLFOXIRI [irinotecan (CPT-11), oxaliplatin (L-OHP) 85 mg/m2, and folinate (LV) 200 mg/m2] on day 1, followed by fluorouracil (5-FU) 3200 mg/m2 infused as a 46-h continuous infusion starting on day 1) repeated every 2 weeks as first-line treatment of RAS wild-type mCRC patients. A decrease in CPT-11 dose was planned (started at level 1: CPT-11 165 mg/m2).

RESULTS:

Seven patients were enrolled, and six were assessed for safety and efficacy. Maximum tolerated dose was not reached at level 1; all patients were treated at these levels. The common Grade 3 or 4 relevant toxicities were diarrhea (50%), hypokalemia (33%) and stomatitis (33%). No treatment-related deaths occurred. Of the six patients assessed four had partial response and the two others had stable disease; hence, the response rate was 66.7% (95% confidence interval 28.9-100%) and the disease control rate was 100%. Time to protocol treatment failure was 7.2 (1.4-7.3) months.

CONCLUSION:

The FOLFOXIRI + panitumumab chemotherapy regimen was well tolerated by our patients with mCRC and showed promising anti-tumor activity. The recommended phase II dose was determined to be the same as the standard doses of this regimen used worldwide.

• Authors: Hironaga Satake, Akihito Tsuji, Masato Nakamura, Masaaki Ogawa, Takeshi Kotake, Yukimasa Hatachi, Hisateru Yasui, Akinori Takagane, Yoshihiro Okita, Kumi Nakamura, Toshihide Onikubo, Masahiro Takeuchi, Masashi Fujii
• Journal: International journal of clinical oncology (Int J Clin Oncol) Vol. 23 Issue 3 Pg. 490-496 (Jun 2018) ISSN: 1437-7772 [Electronic] Japan
• PMID: 29464396 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Organoplatinum Compounds
• Oxaliplatin
• Panitumumab
• Irinotecan
• ras Proteins
• Leucovorin
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Colorectal Neoplasms (drug therapy, genetics, mortality, pathology)
• Female
• Fluorouracil (administration & dosage, adverse effects, therapeutic use)
• Humans
• Irinotecan
• Leucovorin (administration & dosage, adverse effects, therapeutic use)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Organoplatinum Compounds (administration & dosage, adverse effects, therapeutic use)
• Oxaliplatin
• Panitumumab
• Treatment Outcome
• ras Proteins (genetics)