Panitumumab in combination with infusional oxaliplatin and oral capecitabine for conversion therapy in patients with colon cancer and advanced liver metastases

Abstract

BACKGROUND: Preoperative chemotherapy improves the outcome in patients with colorectal cancer with liver metastases. In the current study, the authors evaluated the activity of a conversion treatment with the combination of capecitabine plus oxaliplatin (XELOX) used in association with panitumumab in patients with unresectable, liver-only, metastatic colon cancer. METHODS: Chemotherapy-naive patients with unresectable liver metastases from colon cancer with no other metastatic disease sites were enrolled. All patients received upfront therapy with XELOX plus panitumumab (P-XELOX) and were reevaluated for resectability every 4 cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints were overall survival (OS), progression-free survival, the percentage of patients whose disease became radically resectable, and the safety of the P-XELOX combination. RESULTS: A total of 49 patients were recruited, 35 of whom had wild-type KRAS (wtKRAS) and 14 of whom (who were enrolled before study amendment) had unknown (9 patients) or mutated (5 patients) KRAS mutational status. Forty-six patients were evaluable for response. After conversion P-XELOX therapy, the ORR in the general population was 54%, with 2 complete responses, 23 partial responses, and 14 cases of stable disease. In patients with wtKRAS, the ORR of the patients reached 65% (2 CRs and 19 PRs), which allowed 15 patients with initial unresectable liver metastasis to be reclassified as having resectable disease. Survival analysis demonstrated a median progression-free survival of 8.5 months and a median OS of 21.9 months. Patients who underwent surgery were found to have a significantly better OS when compared with those who did not undergo surgery (P <.001). Overall, toxicities were found to be predictable and manageable, with the most common being cutaneous, gastrointestinal, and neurologic toxicities. CONCLUSIONS: Conversion P-XELOX therapy yields high response and resectability rates for patients with metastatic colon cancer with extensive liver involvement. Cancer 2013;119:3429-35.

Panitumumab in combination with gemcitabine and oxaliplatin does not prolong survival in wild‐type KRAS advanced biliary tract cancer: A randomized phase 2 trial (Vecti‐BIL study)

“…We explored any potential explanation for this survival advantage in IHC patients despite similar PFS. In this subgroup, the median number of cycles was 6 (range, [3][4][5][6][7][8][9][10][11][12] in the P-GEMOX group and 11 (range, 2-12) in the GEMOX group, with more patients in the standard arm completing the preplanned 12-cycle treatment (10 patients in the GEMOX group vs 6 patients in the P-GEMOX group). Moreover, we could not demonstrate any significant difference in the causes of the end of treatment, occurrence of adverse events, second-line treatments, or surgery between the arms (data not shown).…”

Smoothened antagonist GDC-0449 (Vismodegib) inhibits proliferation and triggers apoptosis in colon cancer cell lines

“…While it has been known for hundreds of years, surgical resection and chemotherapy still dominate current regimens and have provided only limited improvement of the 5-year survival rate (4)(5)(6). The current knowledge on the molecular mechanisms of the genesis and progression of colon cancer is limited and its expansion may provide approaches for developing targeted regimens.…”

Deficiency of gap junction composed of connexin43 contributes to oxaliplatin resistance in colon cancer cells

“…Oxaliplatin is one of the most commonly used chemotherapy drugs in colon cancer therapies. It is a third-generation platinum-based anti-neoplastic agent commonly used in the treatment of CRC (15,16). Oxaliplatin application in the clinic has brought about notable improvements in the response rate and progression-free survival in advanced colon cancer, but ~40% of patients still develop resistance (3,17).…”