Comparison of continuously infused 5-fluorouracil with bolus injection in treatment of patients with colorectal adenocarcinoma

Seifert, Paul; Baker, Laurence H.; Reed, Melvin L.; Vaitkevicius, Vainutis K.

doi:10.1002/1097-0142(197507)36:1<123::aid-cncr2820360108>3.0.co;2-c

Cited by 378 publications

(71 citation statements)

References 13 publications

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“…Haematological toxicity was not evaluated, as the patients were discharged from hospital at the time a fall in white cells and platelets would have occurred. Moreover, this form of toxicity is infrequent and asymptomatic when FU is given by continuous infusion at the dosage used (Seifert et al, 1975).…”

Section: Methodsmentioning

confidence: 99%

“…A complete response was defined as the disappearance of all disease; partial response was the objective response as described by Seifert et al (1975) Table I. For the other patients, blood samples were removed at daily intervals.…”

Section: Methodsmentioning

confidence: 99%

“…treatment produce different response rates (Ansfield et al, 1977). Of these regimens, continuous infusion of drug for 5 days is the least toxic (Seifert et al, 1975) and, when combined with other drugs, gives good clinical responses (Woolley et al, 1976). Some data are available on the plasma concentrations of FU after i.v.…”

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confidence: 99%

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Clinical response and plasma levels of 5-fluorouracil in patients with colonic cancer treated by drug infusion

Hillcoat¹,

McCulloch²,

Figueredo³

et al. 1978

Br J Cancer

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Summary.-Concentrations of 5-fluorouracil (FU) were measured in the plasma of patients receiving i.v. infusions of the drug for 5 days as treatment for adenocarcinoma of the gastrointestinal tract. Concentrations of FU varied widely in many patients. Concentration of drug x time of infusion (C x t values) were calculated.Patients showing a partial response or stabilization of disease had significantly higher C x t values than non-responders. Methyl CCNU did not affect the C x t values of FU. Determination of the plasma concentration of FU would allow the dose of the drug to be adjusted to maintain high concentrations of FU in the plasma. Our data suggest that such high concentrations would increase the response rate in this disease.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Clinical response and plasma levels of 5-fluorouracil in patients with colonic cancer treated by drug infusion

Hillcoat¹,

McCulloch²,

Figueredo³

et al. 1978

Br J Cancer

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“…Although the optimal treatment regimen for these two drugs has not been unequivocally defined, the Mayo regimen of 5-FU and low-dose LV is widely regarded as an acceptable treatment and is the only regimen to have demonstrated a significant survival advantage over unmodulated 5-FU (Poon et al, 1989). However, other combination regimens, such as the Machover (5-FU with high-dose LV) regimen (Machover et al, 1986), or continuously infused 5-FU (Seifert et al, 1975;Lokich et al, 1989;de Gramont et al, 1995) are also used.…”

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confidence: 99%

Mature results from three large controlled studies with raltitrexed ('Tomudex')

Cunningham

1998

Br J Cancer

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Summary Since the publication of the results of phase I dose-finding studies, an extensive phase 11 and III clinical study programme has been undertaken to study the clinical efficacy and tolerability of the quinazoline folate analogue raltitrexed ('Tomudex'), a novel direct and specific inhibitor of thymidylate synthase. Two international phase III trials, studies 3 and 12, have compared raltitrexed 3 mg m-2 with 5-fluorouracil (5-FU) plus low-dose leucovorin (LV) (Mayo regimen) or high-dose LV (Machover regimen) respectively. A North American study (study 10) was originally set up to compare two raltitrexed dosage arms (3.0 and 4.0 mg m-2) with 5-FU and low-dose LV, but the 4.0 mg m-2 arm was discontinued prematurely because of excessive toxicity. Minimum follow-up times for studies 3, 10 and 12 were 15.5, 12 and 9 months, respectively (for data other than survival), with corresponding survival follow-up times of 26, 12 and 17 months. Objective response rates were similar for raltitrexed and 5-FU + LV, and palliative improvements were seen to a similar extent with both treatments in all phase III studies. Survival was statistically similar for raltitrexed and 5-FU + LV in both studies 3 and 12. Raltitrexed was, however, associated with inferior survival to 5-FU + low-dose LV in study 10, but there appears to be evidence that this was linked to an unconscious effect on investigator behaviour of early toxicity problems in this trial, in that patients appeared to be withdrawn from raltitrexed treatment without progression or protocolled toxicity. Moreover, it appeared that 5-FU + LV patients were continued on treatment after disease progression.5-FU-based therapy was associated with a higher incidence of mucositis than raltitrexed in all studies, with the attainment of statistical significance in studies 3 and 12. Elevations in hepatic transaminase levels were seen with raltitrexed, but these are thought to be of no clinical significance. Overall, much greater levels of toxicity were seen with 5-FU + LV than with raltitrexed in early treatment cycles. In addition, retrospective UK audit data have shown the monthly cost of raltitrexed therapy to be similar to that of Mayo and continuous infusion 5-FU regimens, and appreciably lower than that of the de Gramont regimen of 5-FU (bolus + 22-h infusion) + high-dose LV. Thus, raltitrexed is an effective alternative to 5-FU-based therapy in patients with advanced colorectal cancer, with an acceptable and, unlike 5-FU, predictable toxicity profile. In particular, patients receiving raltitrexed may benefit from the minimization or avoidance of mucositis, and both patients and healthcare providers may find the convenient administration schedule of the drug advantageous.

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“…SIR,-Several clinical studies agree that intravenous infusion of 5-fluorouracil (5FU) over a period of five days is less toxic than bolus intravenous injections of drug daily for five days (Moertel et al, 1972;Seifert et al, 1975), although there is disagreement about the frequency of response of gastrointestinal tumours so treated (Moertel et al, 1972;Moertel and Reitemeier, 1969).…”

mentioning

confidence: 99%