Phase II Study of Capecitabine in Patients With Fluorouracil-Resistant Metastatic Colorectal Carcinoma

Hoff, Paulo M.; Pazdur, Richard; Lassere, Yvonne; Carter, Susan; Samid, Dvorit; Polito, Diane; Abbruzzese, James L.

doi:10.1200/jco.2004.05.072

Cited by 55 publications

(33 citation statements)

References 20 publications

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“…This is consistent with the observed efficacy of the same regimen when administered to patients with untreated advanced CRC (Rao et al, 2004). The demonstrated activity of capecitabine/MMC in this study contrasts with the lack of response to capecitabine monotherapy seen in a phase II study of 5FU-refractory advanced colorectal cancer (Hoff et al, 2004). Capecitabine/MMC therefore represents a plausible regimen for those patients who are eligible for treatment after failure of two previous regimens.…”

Section: Discussionsupporting

confidence: 84%

Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan

et al. 2005

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Protracted venous infusion 5-fluorouracil (5FU) combined with mitomycin C (MMC) has demonstrated significant activity against metastatic colorectal cancer. Owing to potential synergy based upon upregulation of thymidine phosphorylase by MMC, the combination of capecitabine and MMC may improve outcomes in irinotecan-refractory disease. Eligible patients with progressive disease during or within 6 months of second-line chemotherapy were treated with capecitabine (1250 mg m À2 twice daily) days 1-14 every 3 weeks and MMC (7 mg m À2 IV bolus) once every 6 weeks. A total of 36 patients were recruited, with a median age of 64 years (range 40 -77), and 23 patients (78%) were performance status 0 -1. The objective response rate was 15.2%. In all, 48.5% of patients had stable disease. Median failure-free survival was 5.4 months (95% CI 4.6 -6.2). Median overall survival was 9.3 months (95% CI: 6.9 -11.7). Grade 3 toxicities were palmar-plantar erythema 16.7%, vomiting 8.3%, diarrhoea 2.8%, anaemia 8.3%, and neutropenia 2.8%. No patients developed haemolytic uraemic syndrome. Symptomatic improvement occurred for pain, bowel symptoms, and dyspnoea. Capecitabine in combination with MMC is an effective regimen for metastatic colorectal cancer resistant to 5FU and irinotecan with an acceptable toxicity profile and a convenient administration schedule.

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Section: Discussionsupporting

confidence: 84%

Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan

et al. 2005

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“…Capecitabine has recently been tried as salvage therapy, but the efficacy was not satisfactory. Capecitabine showed no objective response in 5-FU-resistant cancer in a phase II trial (Hoff et al, 2004). Combination with MMC resulted in a response rate of 15% in irinotecan-resistant cancer, but its efficacy fell to 5% when the cancer was resistant to both irinotecan and oxaliplatin.…”

Section: Discussionmentioning

confidence: 99%

“…Our study was designed to show a response rate of 15%, which is quite high considering the activity of infusional 5-FU and capecitabine in chemotherapy exposed patients. Nevertheless, this response rate is currently the minimum response expected from any new agent targeting second-or thirdline treatment for colorectal cancer (Hoff et al, 2004;Gubanski et al, 2005). Treatment schedule of S-1 was another point of consideration.…”

Section: Discussionmentioning

confidence: 99%

A phase II trial of S-1 monotherapy in metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens

et al. 2006

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This is the first phase II study of S-1 monotherapy for patients with metastatic colorectal cancer after failure of both irinotecan-and oxaliplatin-containing regimens. The initial dose of S-1 was 35 mg m À2 , administered twice daily for 14 days every 3 weeks. Treatment was repeated until the occurrence of disease progression. Twenty-eight patients were enrolled. S-1 was administered to 21 patients as third-line therapy and to the remaining seven patients as fourth-line therapy. Of 26 evaluable patients, the overall response rate was 14.3% (95% CI, 0.4 -28.1), and the disease control rate was 42.9% (95% CI, 23.3 -62.4). With a median follow-up period of 227 days, median time to progression and overall survival duration were 91 and 414 days, respectively. The 1-year survival rate of all patients was 60.7%. There was no grade 4 toxicity. Grade 3 haematological toxicities were documented only in two patients. In conclusion, S-1 shows potential as a salvage regimen in heavily pretreated colorectal cancer patients. The twice-daily dose of 35 mg m À2 was well tolerated and can be used in designing further combination chemotherapy.

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“…The efficacy of capecitabine in second-line combinations also might be discussed as illustrated by several recent phase II studies. No response has been obtained in 22 patients of the MD Anderson Cancer Center with 5-FU-resistance (Hoff et al, 2004), and in 51 Korean patients refractory to 5-FU and leucovorin (Lee et al, 2004). The same inefficacy has been observed in 20 Swedish patients who all had received 5-FU, irinotecan and oxaliplatin (Gubanski et al, 2005).…”

Section: Sirmentioning

confidence: 93%

Capecitabine and mitomycin C in patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan

Alliot¹

2006

Br J Cancer

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Sir,In the 5 September issue, Chong et al (2005) reported a phase II study of 36 patients with metastatic colorectal cancer treated with a third-line chemotherapy consisting of capecitabine and mitomycin. The response rate was 15.2%, median failure-free survival, 5.4 months, and median overall survival, 9.3 months. No grade 4 toxicity was observed. Although this regimen seems particularly convenient, the study is questionable by several aspects. The first point is the imprecision regarding prognostic factors. In particular, the number of metastatic sites and several biological factors such as albumin, lactate dehydrogenase, alkaline phosphatase or carcinoembryonic antigen have not been detailed. Moreover, there is no mention about the proportion of patients who have been operated for a primary tumour. Since these patients benefit from a follow-up, early detection of metastases can be favoured, leading to the selection of patients with low tumour burden and finally, to a potential advantage in terms of therapeutic efficacy and tolerance. Another point is the first-line therapy which consisted only of 5-fluorouracil (5-FU) in 33 patients, although only two have had received oxaliplatin. Moreover, there is no precision regarding the type of 5-FU-based regimen since a longer progression-free survival has been clearly demonstrated with the LV5FU2 regimen (bimonthly combination of high-dose leucovorin and 5-FU bolus plus continuous infusion) comparatively with the monthly schedule of low-dose leucovorin and 5-FU (de Gramont et al, 1997). The authors compare favourably this regimen with results of thirdline treatments in randomised phase III studies, while it can be admitted that the patients accrued in phase II studies inevitably are more selected. Another indirect comparison with cetuximab is questionable since targeted therapies offer their best activity in combination with chemotherapy (Cunningham et al, 2004). Conceptually, the probability of response of mitomycin-C after either oxaliplatin or irinotecan is extremely low. Moreover, probably oral fluoropyrimidines will replace 5-FU in a vast proportion of the first-line combinations in advanced diseases, and probably in the adjuvant setting (Twelves et al, 2005). The efficacy of capecitabine in second-line combinations also might be discussed as illustrated by several recent phase II studies. No response has been obtained in 22 patients of the MD Anderson Cancer Center with 5-FU-resistance (Hoff et al, 2004), and in 51 Korean patients refractory to 5-FU and leucovorin (Lee et al, 2004). The same inefficacy has been observed in 20 Swedish patients who all had received 5-FU, irinotecan and oxaliplatin (Gubanski et al, 2005). Finally, a poor response rate of 4.8% has been obtained in 21 Korean patients receiving mitomycin-C and capecitabine as third-line chemotherapy after various combinations of 5-FU, irinotecan and oxaliplatin (Lim et al, 2005). Although toxicity seems moderate, grade 2 stomatitis or grade 2 diarrhoea may deteriorate quality of life. Moreover, pat...

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Phase II Study of Capecitabine in Patients With Fluorouracil-Resistant Metastatic Colorectal Carcinoma

Abstract: Single-agent capecitabine in patients with metastatic colorectal carcinoma refractory to FU showed no objective responses and clinical benefit that was, at best, modest. The use of capecitabine in combination with other treatments in this patient population is under investigation.

Cited by 55 publications

References 20 publications

Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan

Capecitabine and mitomycin C as third-line therapy for patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan

A phase II trial of S-1 monotherapy in metastatic colorectal cancer after failure of irinotecan- and oxaliplatin-containing regimens

Capecitabine and mitomycin C in patients with metastatic colorectal cancer resistant to fluorouracil and irinotecan

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