Time-dependent interactions between 5-fluorouracil and mitomycin C on a human colon carcinoma cell line, HCT-8, in vitro

Russello, Orsolina; Romanini, Antonella; Rosso, Riccardo; Nicolin, A; Sobrero, Alberto

doi:10.1016/0277-5379(89)90273-3

Cited by 28 publications

(11 citation statements)

References 2 publications

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“…The cellular mechanism of the clinically observed synergy between MMC and infusional 5-FU has not been further elucidated, although time-dependent interactions between both drugs on human cancer cell lines have been reported (Russello et al, 1989). In previous trials, MMC was applied either using absolute doses (e.g.…”

Section: Discussionmentioning

confidence: 99%

Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study

et al. 2003

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The aim of this study was to define the maximum tolerated dose (MTD) of bolus mitomycin C (MMC) in combination with 24 hcontinuous infusion of 5-flourouracil (FU) plus folinic acid, and to assess the toxicity and activity in patients with previously treated colorectal and gastric cancer. Escalating doses of MMC starting from 6 mg m À2 in 2 mg m À2 -steps to a maximum of 10 mg m À2 were applied on days 1 and 22, given to fixed doses of 5-FU (2.600 mg m À2 ) as 24 h infusion and folinic acid 500 mg m À2 prior to 5-FU weekly for 6 weeks. At least three patients were treated at each dose level. A total of 16 patients have been included in the phase I study. At the highest dose level (MMC 10 mg m À2 ), grade III thrombocytopenia, dyspnoea, mucositis and diarrhoea were observed in one patient each (17 %). In the phase II study 45 patients, 33 with colorectal cancer and 12 with gastric cancer, 23 patients after failure of first-and 22 patients after at least second-line or subsequent chemotherapy have been treated. Seven partial responses (PR) were registered (16%), one (3%; CI 95% , 0 -16) in colorectal and six (50%; CI 95% , 21 -79%) in gastric cancer patients. In all, 17 (38%) achieved disease stabilisation, 15 colorectal (45%, CI 95% , 28 -64%) and two gastric cancer patients (17%; CI 95% , 2 -48%). The median progression-free survival was 3.1 months (range, 0.9 -9.1) in colorectal and 4.6 months (range, 0.7 -12.4) in gastric cancer. The median overall survival time was 6.6 months (range, 1.9 -15.6) in colorectal and 7.1 months (range, 1.7 -20.8) in patients with gastric cancer. This regimen was considered to be safe and well tolerated for pretreated patients with gastrointestinal adenocarcinoma. In gastric cancer,MMC plus infusional 5-FU/folinic acid may be a potential second-line regimen with promising antitumour activity.

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Section: Discussionmentioning

confidence: 99%

Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study

et al. 2003

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“…The combination of MMC and 5FU has shown synergistic growth inhibition of cell lines (Sartorelli and Booth, 1965), including colorectal cancer cell lines (Russello et al, 1989). A randomised controlled trial in colorectal cancer found that MMC in combination with protracted venous infusion (PVI) 5FU increased the response rates to 54%, but with no benefit to overall and 1-year survival (Ross et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Combination chemotherapy in advanced gastrointestinal cancers: ex vivo sensitivity to gemcitabine and mitomycin C

et al. 2003

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Advanced or metastatic disease is common in both oesophagogastric and colorectal cancers, with poor 5-year survival despite palliative chemotherapy. We have investigated the sensitivity of gastrointestinal tumours to gemcitabine in combination with mitomycin C (GeM), using a modified ex vivo ATP-based tumour chemosensitivity assay (ATP-TCA). Tumour material from 41 colorectal and 22 oesophagogastric cancers were assessed. The GeM combination showed variable but definite activity in most of the samples tested. The results show that GeM achieves 495% inhibition at concentrations within the range achievable clinically in 60% of colorectal tumours (21 out of 35) and 38% of oesophagogastric tumours (five out of 13) tested. We did not identify any significant difference in sensitivity using concurrent or sequential exposure of tumour-derived cells to these two drugs. The results from this study suggest that GeM may be a useful combination in the treatment of advanced gastrointestinal malignancy.

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“…Results in human cancer cell ae ORIGINAL ARTICLE ae lines suggest a supra-additive effect of a combination of 5-fluorouracil and mitomycin C (9). Phase II studies also suggest an improved effect of the combination when 5-fluorouracil is given as a continuous infusion but this was not confirmed in phase II trials (10, 11) with 5-fluorouracil given as i.v.…”

Section: Received 1 October 2003 Accepted 29 January 2004mentioning

confidence: 99%

A phase II study of UFT and leucovorin in combination with mitomycin C in patients with metastatic colorectal cancer

Gyldenkerne

Glimelius²,

Frödin³

et al. 2004

Acta Oncologica

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Time-dependent interactions between 5-fluorouracil and mitomycin C on a human colon carcinoma cell line, HCT-8, in vitro

Cited by 28 publications

References 2 publications

Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study

Protracted infusional 5-fluorouracil plus high-dose folinic acid combined with bolus mitomycin C in patients with gastrointestinal cancer: a phase I/II dose escalation study

Combination chemotherapy in advanced gastrointestinal cancers: ex vivo sensitivity to gemcitabine and mitomycin C

A phase II study of UFT and leucovorin in combination with mitomycin C in patients with metastatic colorectal cancer

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