Oxaliplatin plus raltitrexed and leucovorin-modulated 5-fluorouracil i.v. bolus: a salvage regimen for colorectal cancer patients

Abstract

The aim of the present study was to define the activity and tolerability of a triplet regimen including oxaliplatin 130 mg m 72 (2 h i.v. infusion) and raltitrexed 3.0 mg m 72 (15 min i.v. infusion) given on day 1, followed by levo-folinic acid 250 mg m 72 (2 h i.v. infusion) and 5-fluorouracil 1050 mg m 72 i.v. bolus on day 2, every 2 weeks, in pretreated colorectal cancer patients. From April 1999 to December 2000, 50 patients were enrolled: 26 were males and 24 females, their median age was 63 (range, 43 -79) years; ECOG performance status was 0 in 26 patients, 51 in 24 patients; 26 patients had received previous adjuvant chemotherapy, 40 patients had been exposed to one or two lines of palliative chemotherapy (including irinotecan in 31 cases); 18 patients were considered chemo-refractory. A total of 288 cycles were administered, with a median number of 6 (range 1 -12) courses per patient. A complete response was obtained in three patients, and a partial response in nine patients, giving a major response rate of 24% (95% confidence interval, 13 -38%), while 15 further patients showed a stable disease, for an overall control of tumour growth in 60% of patients. Three complete responses and three partial responses were obtained in patients pretreated with irinotecan (response rate, 19%); among refractory patients, three achieved partial responses (response rate, 13%). After a median follow-up of 18 (range, 10 -30) months, 40 patients showed a progression of disease: the growth modulation index ranged between 0.2 and 2.5: it was 51.33 (showing a significant delay of tumour growth) in 16 (40%) patients. Actuarial median progression-free survival time was 7.6 months, and median survival time was 13.6 months: estimated probability of survival was 55% at 1 year. Main severe toxicity was neutropenia: World Health Organisation grade 4 affected 32% of patients; non-haematological toxicity was mild: World Health Organisation grade 3 diarrhoea was complained of by 8%, and grade 3 stomatitis by 4% of patients; neurotoxicity (according to Lévi scale) was scored as grade 3 in 8% of patients. In conclusion, this regimen was manageable and active as salvage treatment of advanced colorectal cancer patients; it showed incomplete cross-resistance with irinotecan-based treatments, and proved to delay the progression of disease in a relevant proportion of treated patients.

Oxaliplatin Plus Dual Inhibition of Thymidilate Synthase During Preoperative Pelvic Radiotherapy for Locally Advanced Rectal Carcinoma: Long-Term Outcome

“…Postsurgical treatment with OXA and 5-FU/LFA improves the disease-free survival and overall survival (OS) of patients with resected stage III colon cancer (16,17). In addition, the combination of OXA with 5-FU/LFA (18) or RTX (19) showed a significant activity in chemonaive metastatic colorectal cancer patients, and the triplet combination of OXA, RTX, and 5-FU/LFA was tolerated and active also in heavily pretreated patients (20).…”

Biweekly oxaliplatin, raltitrexed, 5-fluorouracil and folinic acid combination chemotherapy during preoperative radiation therapy for locally advanced rectal cancer: a phase I–II study

“…Clinical studies have shown high response rates for the combination of OXA with either FU/FA or RTX in MCRC (Cascinu et al, 2002;Seitz et al, 2002;Goldberg et al, 2004;Comella et al, 2005). Furthermore, the addition of OXA to a biweekly regimen of RTX and FU/FA proved manageable and active in heavily pretreated patients (Comella et al, 2002). Recently, several investigators have reported encouraging results with the addition of OXA to fluoropyrimidines during pelvic preoperative radiotherapy in LARC (Gerard et al, 2003;Rodel et al, 2003;Gambacorta et al, 2004a;Aschele et al, 2005;Sebag-Montefiore et al, 2005).…”

Raltitrexed combined with bevacizumab in heavily pretreated metastatic colorectal cancer

“…In a series of clinical trials, raltitrexed has shown promising efficacy, favorable toxicity profile, and convenient administration schedule in patients with 5-FU-refractory mCRC as second-or third-line regimen. [4,8,9] Bevacizumab has been evaluated in various solid tumors. Several large phase III studies have demonstrated that the addition of bevacizumab to first-or second-line chemotherapy resulted in significant improvement in survival and response among patients with mCRC.…”