Turkish
Albanian
Arabic
Armenian
Azerbaijani
Belarusian
Bengali
Bosnian
Catalan
Czech
Danish
Deutsch
Dutch
English
Estonian
Finnish
Français
Greek
Haitian Creole
Hebrew
Hindi
Hungarian
Icelandic
Indonesian
Irish
Italian
Japanese
Korean
Latvian
Lithuanian
Macedonian
Mongolian
Norwegian
Persian
Polish
Portuguese
Romanian
Russian
Serbian
Slovak
Slovenian
Spanish
Swahili
Swedish
Turkish
Ukrainian
Vietnamese
Български
中文(简体)
中文(繁體)
Clinical Cancer Research 2004-Aug

Phase I and pharmacokinetic study of the oral fluoropyrimidine S-1 on a once-daily-for-28-day schedule in patients with advanced malignancies.

Sadece kayıtlı kullanıcılar makaleleri çevirebilir
Giriş yapmak kayıt olmak
Bağlantı panoya kaydedilir
Quincy Siu-Chung Chu
Lisa A Hammond
Garry Schwartz
Leonel Ochoa
Sun-Young Rha
Louis Denis
Kathleen Molpus
Brian Roedig
Stephen P Letrent
Bharat Damle

Anahtar kelimeler

Öz

OBJECTIVE

The oral fluoropyrimidine S-1, which consists of a mixture of a 5-fluorouracil (5-FU) prodrug (tegafur), a dihydropyrimidine dehydrogenase inhibitor [5-chloro-2,4-dihydroxypyrimidine (CDHP)], and an inhibitor of orotate phosphoribosyltransferase [potassium oxonate (oxonic acid)], was developed to increase the feasibility and therapeutic index of 5-FU administered orally. The principal objective of this study was to assess the feasibility of administering S-1 on a once-daily-for-28-day schedule every 5 weeks, determine the maximum tolerated dose, characterize the pharmacokinetics of S-1, and seek evidence of anticancer activity.

METHODS

Patients with advanced solid malignancies were treated with escalating doses of S-1 on a once-daily oral schedule for 28 days every 5 weeks. The maximum tolerated dose was defined as the highest dose in which fewer than two of the first six new patients experienced dose-limiting toxicity. The pharmacokinetic profiles of the tegafur, CDHP, and oxonic acid constituents were characterized.

RESULTS

Twenty patients were treated with 72 courses of S-1 at three dose levels ranging from 50 to 70 mg/m(2)/day. Diarrhea, which was often associated with abdominal discomfort and cramping, was the principal dose-limiting toxicity of S-1 on this protracted schedule. Nausea, vomiting, mucositis, fatigue, and cutaneous effects were also observed but were rarely severe. Myelosuppression was modest and uncommon. A partial response and a 49% reduction in tumor size were observed in patients with fluoropyrimidine- and irinotecan-resistant colorectal carcinoma. The pharmacokinetic data suggested potent inhibition of 5-FU clearance by CHDP, with resultant 5-FU exposure at least 10-fold higher than that reported from equitoxic doses of tegafur modulated by uracil in the oral fluoropyrimidine UFT.

CONCLUSIONS

The recommended dose for Phase II studies of S-1 administered once daily for 28 consecutive days every 5 weeks is 50 mg/m(2)/day. The pharmacokinetic data indicate substantial modulation of 5-FU clearance by CDHP. Based on these pharmacokinetic data, the predictable toxicity profile of S-1, and the low incidence of severe adverse effects at the recommended Phase II dose, evaluations of S-1 on this schedule are warranted in malignancies that are sensitive to the fluoropyrimidines.

Facebook sayfamıza katılın

Bilim tarafından desteklenen en eksiksiz şifalı otlar veritabanı

  • 55 dilde çalışır
  • Bilim destekli bitkisel kürler
  • Görüntüye göre bitki tanıma
  • Etkileşimli GPS haritası - bölgedeki bitkileri etiketleyin (yakında)
  • Aramanızla ilgili bilimsel yayınları okuyun
  • Şifalı bitkileri etkilerine göre arayın
  • İlgi alanlarınızı düzenleyin ve haber araştırmaları, klinik denemeler ve patentlerle güncel kalın

Bir belirti veya hastalık yazın ve yardımcı olabilecek bitkiler hakkında bilgi edinin, bir bitki yazın ve karşı kullanıldığı hastalıkları ve semptomları görün.
* Tüm bilgiler yayınlanmış bilimsel araştırmalara dayanmaktadır

Google Play badgeApp Store badge