Adjuvant FOLFOX chemotherapy and splenomegaly in patients with stages II-III colorectal cancer.

BACKGROUND: The impact of adjuvant chemotherapy on hepatic function and portal hypertension in patients with stages II-III colon cancer has not been previously described. We conducted a retrospective study to assess the effects of adjuvant FOLFOX chemotherapy on the splenic index (SI) as a surrogate marker for portal hypertension. METHODS: Stage II-III colorectal cancer patients treated with adjuvant FOLFOX or fluorouracil/leucovorin (5-FU/LV) at Roswell Park Cancer Institute between 2002 and 2006 were identified. Computerizedt omography (CT) scans obtained prior to and at completion of chemotherapy, and every 6 months thereafter were reviewed. Splenic size was evaluated using the SI (SI = length x width x height of the spleen). RESULTS: 40 patients were identified in the FOLFOX group and 23 in the 5-FU/LV group. After 6 months of adjuvant chemotherapy, the mean increase in SI was 45.7 and 16.3% in the FOLFOX and 5-FU/LV groups, respectively (p = 0.0069). SI increased by >100% in 6 patients (15%) in the FOLFOX group versus none in the 5-FU/LV group (p = 0.16). The mean SI at completion of adjuvant chemotherapy was significantly higher in the FOLFOX group than in the 5-FU/LV group (p = 0.007). The mean SI decreased steadily over a period of 2 years after discontinuation of FOLFOX, suggesting potential reversibility of oxaliplatin-induced hepatic injury in this setting. CONCLUSIONS: Adjuvant FOLFOX significantly increases the SI in patients with resected colorectal cancer in comparison to adjuvant 5-FU/LV. The increase in SI may be a marker of oxaliplatin-induced hepatic injury and should be investigated further in prospective longitudinal studies of oxaliplatin-based adjuvant chemotherapy.

Concurrent oxaliplatin, 5-fluorouracil, and radiotherapy in the treatment of locally advanced esophageal carcinoma.

PURPOSE: The combination of oxaliplatin, 5-fluorouracil, and leucovorin with concurrent radiotherapy was demonstrated to be a safe regimen for locally advanced esophageal carcinoma in a prior phase I study. We now report the efficacy data for 42 patients treated with this regimen. METHODS: Each chemotherapy cycle lasted 29 days and consisted of 5-fluorouracil, 180 mg/m2 protracted-infusion from days 1 to 29, and oxaliplatin, 85 mg/m2 on days 1, 15, and 29. The first cycle was administered concurrently with radiation. The radiation field included regional lymph nodes as well as the primary tumor or tumor bed to a dose of 50.4 Gy in 28 fractions. After concurrent chemoradiotherapy, 1 to 2 additional cycles of chemotherapy were administered. If esophagectomy was indicated, it occurred 4 weeks after completion of concurrent chemoradiotherapy. In the adjuvant group, concurrent chemoradiotherapy was initiated 4 weeks after surgery. RESULTS: Median age was 61 years (range 38-78 years); 30 (71%) of the patients were male. Thirty-three patients had adenocarcinoma, and 9 had squamous cell carcinoma. Concurrent chemoradiotherapy was administered preoperatively (group 1) in 24 patients, definitively (group 2) in 13 patients, and as adjuvant treatment (group 3) in 5 patients. In group 1, 16 patients were down-staged including 1 patient with minimal residual disease and 5 with a complete pathologic response; 4 patients were not down-staged, and 4 did not undergo esophagectomy (2 progressed, 1 died of unrelated causes, and 1 refused). In group 2, 1 patient had a complete clinical response, 4 others were down-staged, 2 had stable disease, and 6 progressed. Four patients in group 3 progressed. Median survival was 28 months for group 1, 12 months for group 2, and not reached at 14 months for group 3. There was one grade 4 toxicity (anaphylaxis) in group 2. Grade 3 toxicities were reported for 5 patients in group 1 and 1 patient in group 2. They consisted of hypotension (n=1), fatigue (n=2), diarrhea (n=2), neuropathy (n=1), mucositis (n=1), pneumonitis (n=1), dehydration (n=1), emesis (n=1), and weight loss (n=1). CONCLUSIONS: Our study supports the incorporation of oxaliplatin into a multimodal concurrent chemoradiotherapy protocol for locally advanced esophageal cancer.

Cetuximab-induced hypomagnesemia in patients with colorectal cancer.

BACKGROUND: Cetuximab treatment has been associated with severe hypomagnesemia, but the predisposing factors and management of this toxicity have been poorly characterized. PATIENTS AND METHODS: The charts of 114 patients with colorectal cancer treated with cetuximab were reviewed. Forty-eight evaluable patients had normal magnesium levels before initiation of cetuximab and >or=1 repeat magnesium level during cetuximab treatment. The incidence, grade, and management of hypomagnesemia were described in the evaluable population. RESULTS: Among the evaluable population, 13 patients developed grade 3/4 hypomagnesemia (27%). The incidence of grade 3/4 hypomagnesemia was 6%, 23%, and 47% in patients receiving < 3 months, 3-6 months, and > 6 months of cetuximab therapy, respectively. Grade 3/4 hypomagnesemia was refractory to oral supplementation and required daily to 3-times-weekly intravenous magnesium sulfate supplementation at 6-10 g per dose. Recovery or amelioration in hypomagnesemia occurred approximately 4 weeks after cetuximab discontinuation. CONCLUSION: Severe hypomagnesemia is a frequent side effect of cetuximab therapy. Treatment of hypomagnesemia requires frequent intravenous magnesium supplementation and can be associated with significant patient inconvenience and an increased risk of venous access-related complications. Intermittent cetuximab schedules need to be investigated in order to reduce the frequency and severity of hypomagnesemia.