Phase I study of the novel distamycin derivative tallimustine (FCE 24517)

Sessa, Cristiana; Pagani, Olivia; Zurlo, Maria Grazia; Jong, J. de; Hofmann, Claudia; Lassus, M.; Marrari, P.; Benedetti, Μ. Strolin; Cavalli, Franco

doi:10.1093/oxfordjournals.annonc.a058728

Cited by 42 publications

(24 citation statements)

References 11 publications

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“…Studies in other types of cancer are ongoing. Toxicity consisted of a highly selective neutropenia, which confirms the data obtained from phase I studies (Sessa et al, 1994;Abigerges et al, 1993;Hageboutros et al, 1994). A concentrationdependent inhibition of human myeloid progenitor cells has been demonstrated (Volpe et al, 1993).…”

supporting

confidence: 77%

“…Tallimustine is cross-resistant with doxorubicin but not with melphalan and cisplatin, and drug resistance is only partially mediated through mdr-J-p170 (Pezzoni et al, 1991;Geroni et al, 1993;Capolongo et al, 1993). The doselimiting toxicity in phase I studies was a highly selective neutropenia (Sessa et al, 1994;Abigerges et al, 1993;Hageboutros et al, 1994 admissions for treatment with i.v. antibiotics.…”

mentioning

confidence: 99%

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Tallimustine in advanced previously untreated colorectal cancer, a phase II study

Punt

Humblet²,

Roca³

et al. 1996

Br J Cancer

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Summary Tallimustine is a novel benzoyl mustard derivative from distamycin A with a unique mode of action. It is a DNA minor groove binder and produces highly sequence-specific alkylations. Previous studies have shown significant anti-tumour effects in animal models. We performed a phase II study in previously untreated patients with advanced colorectal cancer, using a schedule of i.v. bolus infusions of 900 Mg m 2 once every 4 weeks. Seventeen patients were enrolled, and no responses were documented in 14 evaluable patients. Toxicity mainly consisted of a highly selective neutropenia, which warrants further investigation of this agent in combination with myeloid growth factors.

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supporting

confidence: 77%

mentioning

confidence: 99%

Tallimustine in advanced previously untreated colorectal cancer, a phase II study

Punt

Humblet²,

Roca³

et al. 1996

Br J Cancer

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“…The initial compounds of this class, in spite of the exciting activity shown in preclinical models, did not undergo complete clinical development due to their severe myelotoxicity [8][9][10][11]. Brostallicin is a newer minor groove binder, which was selected for clinical development because of its improved therapeutic index (outstanding clinical activity and a favorable toxicity proWle) in preclinical models [1].…”

Section: Discussionmentioning

confidence: 99%

Phase I dose-escalation study of brostallicin, a minor groove binder, in combination with cisplatin in patients with advanced solid tumors

Caponigro

Lorusso

Fornari³

et al. 2009

Cancer Chemother Pharmacol

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“…In fact, Tallimustine given in a day 1 q 4 weeks schedule had a brief neutropenia as dose-limiting toxicity (Sessa et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Phase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus schedule

et al. 1999

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Carzelesin is a cyclopropylpyrroloindole analogue which acts as a DNA-sequence-specific alkylating agent. In this phase I study, Carzelesin was given as a 4-weekly 10 min IV infusion to 51 patients with advanced solid tumours. Patients received a median of two courses (range 1–5) at one of nine dose levels: 24, 48, 96, 130, 150, 170, 210, 250 and 300 μg m −2 . According to NCI-CTC criteria, non-haematological toxicities (grade 1/2) included fever, nausea and vomiting, mucositis and anorexia, none of which was clearly dose related. The dose-limiting toxicity was haematological and consisted mainly of neutropenia and to a lesser extent thrombocytopenia. From the dose level 150 μg m −2 , the haematological toxicity (particularly thrombocytopenia) was delayed in onset, prolonged and cumulative in some patients. In several courses, double WBC nadirs occurred. The maximum tolerated dose for a single course was 300 μg m −2 . From the dose level 170 μg m −2 , the intended dose intensity could not be delivered to most patients receiving > 2 courses owing to cumulative haematological toxicity. The dose level with the best dose intensity for multiple courses was 150 μg m −2 . The pharmacokinetics of Carzelesin and its metabolites (U-76,073; U-76,074) have been established in 31 patients during the first course of treatment using a HPLC method. Carzelesin exhibited linear pharmacokinetics. The concentration of U-76,074 (active metabolite) extended above the lower limit of quantitation (1 ng ml −1 ) for short periods of time and only at the higher dose levels. There was no relationship between neutropenia and the AUC of the prodrug Carzelesin, but the presence of detectable plasma levels of the active metabolite U-76,074 was usually associated with a substantial decrease in ANC values. © 1999 Cancer Research Campaign

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Phase I study of the novel distamycin derivative tallimustine (FCE 24517)

Cited by 42 publications

References 11 publications

Tallimustine in advanced previously untreated colorectal cancer, a phase II study

Tallimustine in advanced previously untreated colorectal cancer, a phase II study

Phase I dose-escalation study of brostallicin, a minor groove binder, in combination with cisplatin in patients with advanced solid tumors

Phase I study of Carzelesin (U-80,244) given (4-weekly) by intravenous bolus schedule

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