Five Years Clinical Experience with 5-Fluorouracil

Ansfield, Fred J.; Schroeder, John M.; Curreri, Anthony R.

doi:10.1001/jama.1962.03050300015003

Cited by 200 publications

(32 citation statements)

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“…5-FU has been shown to be active against a variety of solid tumors, including breast, colon, rectum and cervix. 8,9) 5-FU is an ideal drug candidate for transdermal delivery into the systemic circulation that mimics the continuous IV route of administration. Woolfson et al 21) have reported that 5-FU bioadhesive patches can been be used for local delivery to uterine cervix in cervical intraepithelial neoplasia (CIN), which is a common and potentially malignant condition affecting women of a wide range of ages.…”

Section: Determination Of the Cytotoxic Concentration Of 5-fu On Dla mentioning

confidence: 99%

“…6, 7) 5-FU has been shown to be active against a variety of solid tumors, including those in breast, colon, rectum and cervix. 8,9) Apart from clinical usefulness for topical treatment of skin-related disorders, transdermal delivery of 5-FU may overcome certain limitations associated with oral and parenteral administration of 5-FU. After oral administration, 5-FU is poorly absorbed with significant variation in bioavailability, ranging between 0 and 80%, while following parenteral administration of 5-FU, there is a rapid elimination of the drug with an apparent terminal half-life of approximately 8-20 min.…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxicity, Anti-tumor Activity, Cumulative Skin Irritation and Sensitization Study of 5-Fluorouracil from a Transdermal Patch for Dalton's Lymphoma Ascites Cells

Chandrashekar

Hiremath

2007

JOURNAL OF HEALTH SCIENCE

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Dalton's lymphoma ascites (DLA) cells were used as a model cell line to evaluate the cytotoxic concentration and anti-tumor activity of 5-fluorouracil (5-FU) through transdermal drug delivery (TDD) for solid tumors. Cytotoxicity was measured by exposing cell suspensions to increased concentrations of drug from 10-50 µg/ml and then the viable cells count was measured by the tryphan blue exclusion method. The results confirmed that 50 µg/ml of 5-FU was cytotoxic to DLA cells. The tumor volume was 0.23 cm 2 and the increase in life span (ILS) was 81.8% with a maximum survival time of 39.5±1.87 days for 5-FU monolithic matrix transdermal patch in mice with solid tumors induced by DLA. The results were significantly different (p < 0.05) compared to the untreated control, which had a maximum survival time of 19±1 days. The anti-tumor activity was very effective compared to intravenous therapy (ILS, 25.58%, maximum survival time, 24±2.7 days). No signs of erythema, vesiculations or bullous reaction were observed with the patches. The mean cumulative skin irritation and adherence scores for both mice and humans were zero and less than one, proving there was no irritation or sensitization. The patches adhered completely to the skin, without leaving any adhesive on skin (score=0 in human subjects). The transdermal patches had 100% flatness, a thickness of 150±0.03 mm, good content uniformity, folding endurance (> 500 foldings), elegance, smoothness, transparency, and flexibility. The Velcro protection jackets were suitable for the study and prevented the mice from licking, scratching, and rubbing the patches.

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Section: Determination Of the Cytotoxic Concentration Of 5-fu On Dla mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytotoxicity, Anti-tumor Activity, Cumulative Skin Irritation and Sensitization Study of 5-Fluorouracil from a Transdermal Patch for Dalton's Lymphoma Ascites Cells

Chandrashekar

Hiremath

2007

JOURNAL OF HEALTH SCIENCE

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“…5-FU alone, administered either as a bolus or by continuous infusion, results in response rates from 15% to 29%. [52][53][54][55] Leucovorin (LV), a modulator of fluoropyrimidine metabolism, has been used in combination with 5-FU in an attempt to enhance its specific efficacy and thereby reduce host toxicity. In most reported series, the combination of 5-FU and LV has produced a response rate significantly better than 5-FU alone (Table 1).…”

Section: Systemic Chemotherapymentioning

confidence: 99%

Management of hepatic metastases

Choti

Bulkley

1999

Liver Transpl

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Although the liver is the most common site of metastatic disease from a variety of tumor types, isolated hepatic metastases most commonly occur from colorectal cancer and, less frequently, from neuroendocrine tumors, gastrointestinal sarcoma, ocular melanoma, and others. Complete evaluation of the extent of metastatic disease, both intrahepatically and extrahepatically, is important before considering treatment options. Based on a preponderance of uncontrolled studies for hepatic metastatic colorectal carcinoma, surgical resection offers the only potential for cure of selected patients with completely resected disease, with 5-year survival rates of 25% to 46%. Systemic and hepatic arterial infusion chemotherapy may be useful treatment options in patients with unresectable disease and possibly as an adjuvant treatment after liver resection. Other techniques of local tumor ablation, including cryotherapy and radiofrequency ablation, although promising, remain unproved. Management of hepatic metastases from neuroendocrine tumors and other noncolorectal primary tumors should be individualized based on the patient's clinical course, extent of disease, and symptoms. Copyright 1999 by the American Association for the Study of Liver DiseasesA s many as 50% of the patients with a primary malignancy will eventually develop metastases in the liver, a percentage greater than for any other organ, including the lung. Although primary tumors that drain principally into the portal circulation are more likely than others to develop hepatic metastases, many tumors arising in other sites, such as the breast and lung, also commonly develop hepatic metastases. Although the liver represents a common site of spread from many of these solid tumors, isolated hepatic metastases most commonly occur from colorectal and neuroendocrine tumors. Other less common malignancies also can metastasize predominantly to the liver. For most other solid malignancies, the pattern of metastatic disease is most often that of generalized dissemination. Colorectal MetastasesCancer of the colon and rectum is the third most commonly diagnosed cancer in the United States. An estimated 131,600 new cases will have been discovered in 1998, comprising 11% of new cancer diagnoses. 1 An estimated 56,500 deaths will occur from colorectal cancer that year, comprising 10% of all cancer deaths. 1 Although mortality from largebowel cancer has been improving over the past 30 years, largely because of improvements in early detection, diagnosis, and treatment, approximately 50% of the patients with colorectal cancer eventually die of their neoplastic disease. 1 The liver is the most commonly involved organ in patients with metastatic colorectal cancer. Approximately 20% of these patients have clinically recognizable liver metastases at the time of their primary diagnosis. 1,2 After resection of a primary colorectal cancer in the absence of apparent metastatic disease, approximately 50% of the patients will subsequently manifest metastatic liver disease. Given these figures,...

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“…Although 5-FU is considered an inactive drug in the treatment of NHL (Heidelberger, 1982), the total number of patients treated and subsequently reported is small, and the earlier literature does in fact show some responses (Ansfield et al, 1962;Krivit & Bentley, 1960 Table I. Two had diffuse large cell lymphoma, and two well differentiated diffuse lymphocytic lymphoma.…”

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confidence: 99%

DNA flow cytometric study of 5-fluorouracil used to treat end stage non-Hodgkin's lymphoma

Hedley¹

1987

Br J Cancer

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Five Years Clinical Experience with 5-Fluorouracil

Cited by 200 publications

References 2 publications

Cytotoxicity, Anti-tumor Activity, Cumulative Skin Irritation and Sensitization Study of 5-Fluorouracil from a Transdermal Patch for Dalton's Lymphoma Ascites Cells

Cytotoxicity, Anti-tumor Activity, Cumulative Skin Irritation and Sensitization Study of 5-Fluorouracil from a Transdermal Patch for Dalton's Lymphoma Ascites Cells

Management of hepatic metastases

DNA flow cytometric study of 5-fluorouracil used to treat end stage non-Hodgkin's lymphoma

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