The American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium was held January 22-24, 2010 in Orlando, Florida. Cutting edge research on management of colorectal cancer (CRC), symptom management and treatment updates on additional gastrointestinal cancers was presented. Several of the abstracts are reviewed here:
Abstract # 283
Randomized phase III study of panitumumab (pmab) with FOLFOX4 compared to FOLFOX4 alone as first-line treatment (tx) for metastatic colorectal cancer (mCRC): PRIME trial. (Panitumumab Randomized Trial In Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy)
Siena S, Cassidy J, Tabernero J, et al.
Pmab is currently approved as a single agent therapy for patients with chemorefractory mCRC. The PRIME trial aimed to examine the efficacy and safety of FOLFOX4 +/- pmab as first-line therapy for mCRC. Patients were randomized to receive pmab with FOLFOX4 (arm 1) vs FOLFOX4 (arm 2) alone; patients had mCRC with no prior therapy for advanced disease and had no prior oxaliplatin therapy. The endpoint was progression free survival (PFS). Of the 1,183 patients, 93% had evaluable KRAS results 656 (60%) wild-type (WT) and 440 (40%) mutant type (MT). For patients with WT KRAS, the median PFS was 9.6 months for arm 1 patients and 8.0 months for arm 2; for patients with MT KRAS, median PFS was 7.3 months for arm 1 patients and 8.8 months for arm 2. Adverse events were comparable across both arms except for anti-EGFR side effects in arm 1. The authors conclude that pmab significantly improves PFS and is well tolerated in first line therapy of patients with WT KRAS mCRC; PFS was poorer for patients with MT KRAS patients receiving pmab. The study results also confirm the importance of KRAS in determining appropriate patients for treatment with epidermal growth factor inhibitor (EGFRI) agents.
Abstract # 284
Efficacy findings from a randomized phase III trial of capecitabine plus oxaliplatin versus bolus 5-FU/LV for stage III colon cancer (N016968): No impact of age on disease-free survival (DFS)
Haller DF, Cassidy J, Tabernero J, et al.
Haller and colleagues reported on efficacy findings from a randomized phase III trial of capecitabine plus oxaliplatin versus bolus 5-fluorouracil/leucovorin (5-FU/LV) for stage III colon cancer (NO16968). The study examined disease free survival (DFS) across age groups with the patients randomized to either XELOX (capecitabine and oxaliplatin) or bolus IV 5-FU/LV regimens. A total of 1,886 patients were randomized and evaluable for DFS. After a median follow-up of 57 months, DFS was significantly superior for XELOX at 3, 4, and 5 years and the 3 year DFS of patients <70 and >70 showed a similar benefit for XELOX versus 5-FU/LV. The authors concluded that XELOX is superior to bolus 5-FU/LV for DFS as an adjuvant therapy for patients with stage III colon cancer and significantly, efficacy benefits are maintained in patients > 70 years of age, which differs from previous data from the ACCENT (Adjuvant Colon Cancer Endpoints Trial) and MOSAIC data. (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer)
Abstract # 286
Use of a simple blood test evaluating the level of CD24 protein to detect subjects with adenomas
Kraus S, Naumov I, Kazanov D, et al.
CD24 (a cell surface protein and P-selectin ligand) is associated with CRC. This study aimed to evaluate CD24 protein expression in peripheral blood lymphocytes (PBLs) from normal, adenoma, and CRC subjects. The study initially examined 150 consecutive subjects who underwent colonoscopy and had PBLs isolated from blood samples and protein extracts. A second validation trial examined 73 consecutive subjects. In the first analysis, 63 patients had CRC,19 adenomas and 68 normal colonoscopy exams. The sensitivity and specificity of the CD24 test in distinguishing CRC from normal tissue was 70.5% (95% CI, 54.8-83.2%) and 83.8% (95% CI, 74.6-92.7); for detection of advanced adenomas it was 84.2% (95% CI, 60.4-96.4%) and 73.5% (95% CI, 61.4-83.5%). Data from the second trial were improved. The authors conclude that this blood test is the first to detect adenomas and can discriminate between CRC and normal tissue, potentially serving as a promising new blood biomarker for early detection of CRC and surveillance of disease
Abstract # 289
Serum 25-hydroxy vitamin D (vit D) and survival in colorectal cancer (CRC): A retrospective analysis.
Wesa KM, Cronin NH, Segal L, et al.
Vit D levels are associated with CRC, with higher levels linked to a decreased incidence of the disease. Normal vit D levels of 40-60 ng/ml are important for bone health. This retrospective study from Memorial Sloan Kettering Cancer Center (MSKCC) examined stored sera from CEA measurements for baseline vit D levels in newly diagnosed stage IV CRC patients. The authors wished to determine whether or not serum vit D levels at diagnosis predict survival. 250 patients with CEAs drawn within 30 days of stage IV CRC diagnosis and available survival data were included in this analysis. The study found that 153 of the 250 patients had died as of April, 2009. Univariate analysis showed vit D was significantly associated with survival when analyzed as a continuous variable (P=0.036). Patients with vit D deficiency (< 30 ng/ml) had survival outcomes approximately 1.5 times worse than patients with normal levels, with the median vit D level for all 250 patients 21.5 ng/ml. Vit D deficiency (< 30 ng/ml) was found in 83% of the patients and only seven patients had serum vit D levels of > 40 ng/ml. The authors conclude that a majority of patients with newly diagnosed stage IV CRC are vit D deficient when diagnosed, and that higher levels of vit D at diagnosis are linked to improved overall survival.
Abstract # 345
Picoplatin/5-fluorouracil/leucovorin (FOLPI) versus modified FOLFOX-6 as first-line therapy for colorectal cancer (CRC).
Earhart RH, Cheporov SV, Gladkov O, et al.
Neurotoxicity is the dose-limiting side effect for oxaliplatin, an integral treatment for advanced CRC. A randomized phase II study was evaluated using picoplatin (pico), a platinum agent, with 5-FU/LV versus modified FOLFOX-6 (FOLFOX) in the first-line treatment of patients with advanced CRC. Tumor response and adverse events were evaluated in the study; 51 patients received FOLPI; 50 received FOLFOX. Although FOLFPI had significantly less grade 2-4 neurotoxicity, neutropenia (57%) and thrombocytopenia (43%) were seen more frequently versus FOLFOX (43% and 12%). Drug-related adverse events causing withdrawal from the study occurred equally in both arms (20%). FOLPI produced similar disease control and survival rates compared to FOLFOX with less neurotoxicity. The hematologic toxicity was considered manageable with FOLPI.
Abstract # 468
A randomized trial of two different doses of pyridoxine in the prevention of capecitabine-associated palmar-plantar erythrodysesthesia.
Chalermchai T, Sriuranpong V.
Palmar-plantar erythrodysesthesia (PPE) is a dose-limiting side-effect of capecitabine, an effective therapy for colorectal cancer (CRC). Limited strategies exist to manage and prevent PPE with capecitabine. 56 patients were studies with breast or colorectal cancer receiving single-agent capecitabine and randomly assigned to receive either 200 or 400 mg of pyridoxine daily for prophylaxis of PPE. The patients receiving high-dose pyridoxine had less PPE compared to the low-dose arm (39.3% vs 71.3%), with severe grade III PPE in 3/28 low dose patients versus none in the high-dose arm. The authors conclude that 400 mg of pyridoxine daily is more effective in preventing PPE with capecitabine compared to the conventional 200 mg daily dose.
Full text for the above abstracts and all other abstracts presented at the symposium may be viewed here.
The 2010 ASCO GI Symposium is available via Virtual Meeting and Podcast. Member and non-members are invited. To view, visit the ASCO Bookstore located here.