Etretinate in Treatment of Actinic Keratosis

Moriarty, M.; Dunn, J.; Darragh, A.; Lambe, R.; Brick, Irving B.

doi:10.1016/s0140-6736(82)91393-9

Cited by 126 publications

(28 citation statements)

References 4 publications

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“…In the past decade, several studies have demon-stratcd the effectiveness of retinoids in the prevention of skin cancer in certain risk groups, namely patients with extensive keratosis actinica [5], xeroderma pigmentosum [6], basal cell naevus syndrome |6], and also in renal trans plant recipients [7|. Although a minor influence was noted on existing tumors, there was an evident tumor-preventive effect as long as the retinoid was given.…”

Section: Discussionmentioning

confidence: 99%

Acitretin as Cancer Chemoprophylaxis in a Renal Transplant Recipient

Vandeghinste

Bersaques²,

Geerts³

et al. 1992

Dermatology

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Section: Discussionmentioning

confidence: 99%

Acitretin as Cancer Chemoprophylaxis in a Renal Transplant Recipient

Vandeghinste

Bersaques²,

Geerts³

et al. 1992

Dermatology

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“…Thus, retinoids have been reported to be active in several skin diseases such as actinic keratosis (Moriarty et al, 1982), oral leucoplakia (Hong et al, 1986) and xeroderma pigmentosum (Kraemer et al, 1988). They were also shown to induce differentiation and to inhibit cell growth in various types of cancers both in vitro and in vivo (Lippman et al, 1987a,b).…”

mentioning

confidence: 99%

Antiproliferative effects of the arotinoid Ro 40-8757 in human gastrointestinal and pancreatic cancer cell lines: combinations with 5-fluorouracil and interferon-α

Louvet

Djelloul²,

Me³

et al. 1996

Br J Cancer

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Summary The arotinoid Ro 40-8757 was previously shown to inhibit the growth of a variety of human cancer cell lines derived from breast, lung and uterus. In view of the high incidence of human digestive cancers, and the slow progress in the development of new therapy, we examined in this paper several combinations between the new arotinoid Ro 40-8757, 5-fluorouracil (5FU) and interferon a-2a on the growth of nine human cancer cell lines derived from the gastrointestinal and pancreatic system. Half-maximal inhibition of cell proliferation by Ro 40-8757 was observed at concentrations ranging between 0.18 and 0.57 um, and increased up to 4.7 gM in retinoid-resistant CAPAN 620 pancreatic cells. All-trans-retinoic acid was 70 times less potent. The sensitivity of HT29-5FU-resistant colonic cells was similar to that observed in the parental cells, suggesting an action independent of pyrimidine metabolism. Ro 40-8757 did not induce any differentiation on HT29 cells, as suggested by ultrastructural analysis. The arotinoid did not interact with receptor signal transduction pathways under the control of serum components, such as growth factors as half-maximal inhibition of growth was similar in HT29-S-B6 cells cultured in the absence or presence of serum. Cell cycle analysis showed that Ro 40-8757 was not acting at a phase-specific transition in HT29 cells and, accordingly, did not induce overexpression of the protein kinase C (PKC)a isoform, or conversion of hyperphosphorylated p105 Rb into hypophosphorylated forms. However, the arotinoid induced significant accumulation of the dephosphorylated, active form of the tumour-suppressor protein. Combinations of Ro 40-8757 with 5FU and interferon a2a resulted in an additive but not synergistic antiproliferative action in HT29 cells. Our data support the interest in Ro 40-8757 as a potent anti-cancer drug, especially in combination therapy with 5FU and interferon, in gastrointestinal and pancreatic cancers, where new active therapeutic modalities are urgently needed.

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“…In summary, the synthetic retinoids isotretinoin and etretinate [4,5,9] are effec tive in the chemotherapy of actinic keratoses and keratoacanthoma, as well as in the chemoprevention of basal cell carcinoma and keratoacanthoma [3-5, 9, 11-15]. The need for chronic maintenance therapy for chemoprevention is demonstrated in this report and others cited above.…”

Section: Discussionmentioning

confidence: 62%

“…Natural and synthetic retinoids arc being studied in the following areas of der matológica oncology: (1) treatment of ex isting skin cancers [1][2][3][4][5][6][7]; (2) treatment of precanccrous conditions such as actinic ker atoses, alone or in combination with other agents [5,[8][9][10], and (3) prevention of cancer and precancer in at-risk populations [11][12][13][14][15] (patients with skin that has been severely damaged by sunlight and pa-dents with a history of skin cancer or pre cancer).…”

Section: Introductionmentioning

confidence: 99%

Long-Term Retinoid Therapy Is Needed for Maintenance of Cancer Chemopreventive Effect

Peck¹

1987

Dermatology

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Two patients with multiple basal cell carcinomas, due either to the nevoid basal cell carcinoma syndrome (NBCCS) or arsenical insecticide exposure, were treated with oral isotretinoin for 7 or 8 years, respectively. Gradually decreasing dosage levels were employed. During the initial courses of therapy, high doses (2.0–3.0 mg/kg/day) were intended as chemotherapy. In these patients only 6 of 40 (15%) lesions underwent complete clinical regression. In subsequent courses aimed at chemoprevention, the dose was progressively reduced from 1.5 to 0.25 mg/kg/day. During therapy, no new lesions were observed in the patient with the arsenical exposure. The NBCCS patient developed 1 new lesion during therapy at 1.0 mg/kg/day, 1 new lesion at 0.5 mg/kg/day and 5 new lesions at 0.25 mg/kg/day. Treatment was discontinued and the patient with the arsenic exposure developed his first new tumor 17 months afterwards; in contrast, the NBCCS patient developed 29 tumors within 13 months. These findings suggest that long-term therapy with isotretinoin is needed for the continuation of the cancer chemopreventive effect. However, the need for continuous rather than intermittent maintenance therapy, and the determination of the optimal dose for this purpose may depend on the etiology of the multiple carcinomas and on the tolerability of the lowest effective dose by the individual patient. With these encouraging data, it now appears appropriate to expand this pilot study and perform larger trials to dertermine the usefulness of isotretinoin in the chemoprevention of basal cell carcinoma in patients with multiple tumors.

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Etretinate in Treatment of Actinic Keratosis

Cited by 126 publications

References 4 publications

Acitretin as Cancer Chemoprophylaxis in a Renal Transplant Recipient

Acitretin as Cancer Chemoprophylaxis in a Renal Transplant Recipient

Antiproliferative effects of the arotinoid Ro 40-8757 in human gastrointestinal and pancreatic cancer cell lines: combinations with 5-fluorouracil and interferon-α

Long-Term Retinoid Therapy Is Needed for Maintenance of Cancer Chemopreventive Effect

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