Clinical studies of triethylenethiophosphoramide in the treatment of inoperable cancer

Shay, Harry; Sun, David C. H.

doi:10.1002/1097-0142(1955)8:3<498::aid-cncr2820080310>3.0.co;2-m

Cited by 46 publications

(8 citation statements)

References 10 publications

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“…Thiotepa ( N , N ′, N ″-triethylenethiophosphoramide) is an alkylating agent that has been used to treat solid tumors and hematological diseases since the 1950s [1, 2]. In vitro studies suggest that thiotepa is metabolized by cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2B6 (CYP2B6) to triethylene phosphoramide (TEPA) [3], which shows a comparable alkylating activity to the parent drug [4].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of thiotepa in high-dose regimens for autologous hematopoietic stem cell transplant in Japanese patients with pediatric tumors or adult lymphoma

Kondo

Ikeda

Goto

et al. 2019

Cancer Chemother Pharmacol

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PurposeThiotepa is used in high-dose chemotherapy (HDT) before autologous hematopoietic stem cell transplantation (HSCT) to treat solid tumors and hematological malignancies. This Phase 1 study was conducted to establish the pharmacokinetics (PK) of thiotepa in a Japanese population.MethodsHDT/HSCT was performed in pediatric patients (≥ 2 years) with solid tumors or brain tumors (thiotepa 200 mg/m2/day IV-infused over 24 h on HSCT Days − 12, − 11, − 5, and − 4 and melphalan 70 mg/m2/day IV-infused over 1 h on Days − 11, − 5, and − 4) and adult patients (≥ 16 years) with malignant lymphoma (thiotepa 200 mg/m2/day 2-h IV-infusion on HSCT Days − 4 and − 3 plus busulfan 0.8 mg/kg 2-h IV-infusion every 6 h from HSCT Days − 8 to − 5). Pharmacokinetics of thiotepa were assessed following initial dose. Safety and efficacy were also evaluated.ResultsNine pediatric and 10 adult patients were enrolled. Mean volume of distribution (Vz) of thiotepa normalized with body surface area (BSA) was lower for pediatric patients (16.4 L/m2) compared with adult patients (26.4 L/m2) as expected due to the higher specific surface area of children. Clearance and biological half-life were similar between pediatric and adult patients. Two serious adverse events (cardiac arrest and pulmonary edema) were observed. Survival rate (Day 100 post-HSCT) was 77.8% (95% CI 36.5–93.9%) for pediatric patients and 100% for adult patients.ConclusionThiotepa elimination was comparable in pediatric and adult patients with cancer. Lower Vz in pediatric compared with adult patients was expected. HDT with thiotepa prior to autologous HSCT was well tolerated.Study registrationJapic CTI-163433.Electronic supplementary materialThe online version of this article (10.1007/s00280-019-03914-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of thiotepa in high-dose regimens for autologous hematopoietic stem cell transplant in Japanese patients with pediatric tumors or adult lymphoma

Kondo

Ikeda

Goto

et al. 2019

Cancer Chemother Pharmacol

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“…Trimethylcolchicinic acid, methyl ether, d-tartrate (TMCA) has been suggested to be A synthetic compound which underwent very limited phase I1 trials (Table XIII) is Preliminary results of early clinical trials have indicated that cis-dichlorodiammine Evaluation of VM-26 is also essentially based on a broad phase I1 trial (86), where 13,26 No activity detected in series of less than 14 patients against tumors of the brain (3,23,27), esophagus (2,13), head and neck (3,ll-13,15,23), kidney (3,8,11,12,23), pancreas (8,11,15), sarcoma (3,23), testicle (3,5,15), and uterus (5,7,15). No activity detected in series of less than 14 patients against tumors of the breast (39,40,44), cervix (35), colon (35,40), esophagus (40), kidney (38,40), melanoma (43), stomach (40), and testicle (38,39,44).…”

Section: Azotomycin or Duazomycin B Belongs To The Class Of Azo-type mentioning

confidence: 99%

Overview of early and investigational chemotherapeutic agents in solid tumors

Rozencweig

Slavik

Muggia

et al. 1976

Med. Pediatr. Oncol.

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“…Others 9 have noted improvement in the form of reduction in tumor size, but such responses have been of short duration.…”

Section: Malignant Melanomamentioning

confidence: 99%

“…Shay found little response in seven cases. 9 Bateman re¬ ported subjective improvement in the ma¬ jority of patients; and objective changes, including reduction in size of peripheral métastases and change in character of effu¬ sion fluids, were observed in 3 of 10 cases treated.1,3…”

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Use of Triethylene Thiophosphoramide (Thio-TEPA) in Treatment of Advanced Cancer

Anderson¹

1957

Arch Surg

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Clinical studies of triethylenethiophosphoramide in the treatment of inoperable cancer

Cited by 46 publications

References 10 publications

Pharmacokinetics of thiotepa in high-dose regimens for autologous hematopoietic stem cell transplant in Japanese patients with pediatric tumors or adult lymphoma

Pharmacokinetics of thiotepa in high-dose regimens for autologous hematopoietic stem cell transplant in Japanese patients with pediatric tumors or adult lymphoma

Overview of early and investigational chemotherapeutic agents in solid tumors

Use of Triethylene Thiophosphoramide (Thio-TEPA) in Treatment of Advanced Cancer

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