Search

Background This analysis assesses the efficacy and safety of a modified FOLFOX (oxaliplatin/leucovorin [LV]/5-fluorouracil [5-FU]) regimen given with a low dose of LV. Patients and Methods Forty patients with previously untreated metastatic colorectal cancer were enrolled to receive every-2-week cycles of oxaliplatin 100 mg/m2 intravenously administered over 2 hours concurrently with LV 20 mg/m2 bolus and 5-FU 400 mg/m2 bolus, followed by a 46-hour infusion of 5-FU 2.4 g/m2. Results Thirty-nine patients received ≥ 1 oxaliplatin dose and a median of 10 treatment cycles (range, 1–13 cycles). Thirteen patients (34%) experienced grade 3/4 neutropenia, whereas 21% of patients experienced grade 3 neurotoxicity. Of 37 eligible patients, complete or partial responses were observed in 18 patients (49% [95% confidence interval (CI), 32%–66%]). The median progressionfree survival was 6.2 months (95% CI, 5.5–8.7 months) with a median overall survival of 14.2 months (95% CI, 10–20.5 months). Conclusion A modified schedule of FOLFOX using a lower than standard dose of LV provides good response and survival results with excellent safety. A comparison with a previous study undertaken in the same centers using identical inclusion/exclusion criteria but using higher doses of LV suggests that reducing the dose of LV improves safety without compromising efficacy.

Background Mismatch repair deficiency (dMMR) has been shown to confer a superior prognosis and is possibly predictive of a lack of benefit from fluoropyrimidine adjuvant chemotherapy (AC) for early-stage colon cancer (ESCC). We conducted a survey to assess medical oncologists' views regarding ESCC AC, with an emphasis on the use of MMR status to guide their recommendations. Materials and Methods The survey was distributed to all members of the Medical Oncology Group of Australia. Their demographic data, practice information, and views on the use of MMR status in ESCC and in 3 case scenarios were collected. The 3 case scenarios were a 68-year-old woman with moderate-risk stage II disease, who was eager to undergo AC (case 1); a 43-year-old woman with high-risk stage II disease, who was ambivalent regarding AC (case 2); and a 78-year-old woman with multiple comorbidities and high-risk stage II disease, who was eager to undergo AC. Results The survey response rate was 35% (190 of 550). Of the 190 responders, 152 (80%) routinely treated patients with colon cancer (CC) and completed the survey. For patients with stage II CC, 112 of 141 (79%) would use MMR status to assist AC recommendations, and 97 (69%) thought it changed their practice. In the case scenarios, 81% (case 1, 110 of 136), 67% (case 2, 92 of 137), and 43% (case 3, 57 of 133) used MMR status to assist AC recommendations. If dMMR was present, 78% (case 1, 86 of 110), 53% (case 2, 49 of 92), and 53% (case 3, 30 of 57) changed their initial recommendations by advising against AC. Conclusion The use of MMR status to assist AC recommendations for patients with stage II CC is an accepted practice for most Australian medical oncologists who responded to our survey.

BACKGROUND: Sensory neurotoxicity is dose limiting for oxaliplatin, an effective drug in the treatment of colorectal cancer (CRC) and other malignancies. This study assessed the impact of gabapentin on oxaliplatin dose intensity and neurotoxicity. PATIENTS AND METHODS: Patients with previously untreated metastatic CRC were recruited sequentially to 2 cohorts: the first used a modified FOLFOX6 (fluorouracil/leucovorin/oxaliplatin) regimen alone with oxaliplatin 100 mg/m(2) every 2 weeks (mFOLFOX; n = 40), and the second included the addition of gabapentin (mFOLFOX+G; n = 41). Gabapentin commenced at 300 mg daily, increasing to a maximum of 600 mg 3 times daily to decrease neurotoxicity. RESULTS: Doses of gabapentin were increased in 31 of 41 patients, with 39% of patients receiving >or= 900 mg daily. The median relative dose intensity of oxaliplatin and requirement for dose reductions or delays because of neurotoxicity were similar in the 2 cohorts. There was no grade 4 neurotoxicity. Whereas grade 3 neurotoxicity was observed in 10% of patients treated with gabapentin versus 21% of patients treated with mFOLFOX alone, there was no statistically significant difference in the severity of neurotoxicity between the 2 cohorts (P = 0.89) or the time to recover from grade 2/3 neurotoxicity (P = 0.97). There were also no significant differences in nonneurologic toxicity or antitumor efficacy between the 2 cohorts. CONCLUSION: This study does not support a role for gabapentin in reducing the incidence or severity of oxaliplatin-induced sensory neurotoxicity.

Most patients with colorectal cancer (CRC) who have failed initial 5-fluorouracil (5-FU) chemotherapy have worsening of disease-related symptoms (DRS) and quality of life (QOL). Irinotecan has a reported response rate of 10%-20% in such patients. The aim of this phase II trial was to prospectively determine the palliative benefit of irinotecan utilizing DRS as primary endpoints of response. Patients had advanced CRC refractory to 5-FU with at least 1 DRS defined as (1) Karnofsky performance status (KPS) 60%-80%, (2) baseline analgesic use > or = 10 mg morphine/day (or equivalent), or (3) disease-related pain score > 1 cm on a 10-cm linear analogue self-assessment (LASA) scale. Patients received irinotecan 125 mg/m2 weekly for 4 weeks on an every-6-weeks schedule. The primary endpoint was palliative response defined as > or = 50% decrease in pain score or analgesic usage, or 10% increase in KPS, from baseline for 4 weeks. QOL was assessed by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) version 2 instrument. A total of 65 patients were entered onto the study. Median baseline parameters were KPS 70%, analgesic score 11 mg/day, and pain score 2.4 cm. A palliative response was achieved in 27 patients (42%), improvement in pain score predominated. LASA and EORTC QLQ-C30 instruments showed parallel changes in DRS. The radiological response rate was 11% (complete responses and partial responses, n = 46); 23 patients achieved stable disease. Median overall survival was 7.2 months. Irinotecan provides a rate of palliative benefit higher than the radiological response rate. Patients-oriented palliative endpoints can be useful in assessing the benefit of agents in early-phase clinical trials.