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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2014

01-12-2014 | Original Article

Phase I study of intravenously administered ATI-1123, a liposomal docetaxel formulation in patients with advanced solid tumors

Authors: Devalingam Mahalingam, John J. Nemunaitis, Laeeq Malik, John Sarantopoulos, Steven Weitman, Kamalesh Sankhala, Jessica Hart, Ahmed Kousba, Nicole S. Gallegos, Gavin Anderson, John Charles, Jon M. Rogers, Neil N. Senzer, Alain C. Mita

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2014

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Abstract

Purpose

ATI-1123 is a liposomal formulation of docetaxel and may be administered without the premedications and hypersensitivity reactions. This Phase I study examines the safety, tolerability, pharmacokinetics (PKs), and antitumor activity of ATI-1123.

Methods

Patients with advanced solid malignancies received escalating doses of ATI-1123 intravenously over 1-h every 3 weeks. The dosing commenced using an accelerated titration design and was followed by a modified 3 + 3 Fibonacci schema to determine maximally tolerated dose (MTD). Plasma was analyzed for encapsulated/non-encapsulated docetaxel; PK analyses were performed using model independent method. Response was assessed using RECIST criteria.

Results

In total, 29 patients received doses ranging from 15 to 110 mg/m2. At 110 mg/m2, two of six patients experienced dose-limiting toxicities including grade 3 stomatitis and febrile neutropenia. The 90 mg/m2 cohort was expanded to ten patients and identified as the MTD. The most common adverse events were fatigue, nausea, neutropenia, anemia, anorexia, and diarrhea. ATI-1123 exhibited linear and dose proportional PKs. One patient with lung cancer had confirmed partial response, and stable disease was observed in 75 % patients.

Conclusions

ATI-1123 demonstrated an acceptable tolerability and favorable PK profile in patients with solid tumors. Our results provide support for Phase II trials to determine the antitumor activity of this drug.
Literature
1.
Dumontet C, Sikic BI (1999) Mechanisms of action of and resistance to anti-tubulin agents: microtubule dynamics, drug transport, and cell death. J Clin Oncol 17(3):1061–1070PubMed
2.
Ajani JA, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Marabotti C, Van Cutsem E (2007) Clinical benefit with docetaxel plus fluorouracil and cisplatin compared with cisplatin and fluorouracil in a phase III trial of advanced gastric or gastroesophageal cancer adenocarcinoma: the V-325 Study Group. J Clin Oncol 25(22):3205–3209. doi:10.​1200/​jco.​2006.​10.​4968 PubMedCrossRef
3.
Blohmer JU, Schmid P, Hilfrich J, Friese K, Kleine-Tebbe A, Koelbl H, Sommer H, Morack G, Wischnewsky MB, Lichtenegger W, Kuemmel S (2010) Epirubicin and cyclophosphamide versus epirubicin and docetaxel as first-line therapy for women with metastatic breast cancer: final results of a randomised phase III trial. Ann Oncol 21(7):1430–1435. doi:10.​1093/​annonc/​mdp585 PubMedCrossRef
4.
Burstein HJ, Manola J, Younger J, Parker LM, Bunnell CA, Scheib R, Matulonis UA, Garber JE, Clarke KD, Shulman LN, Winer EP (2000) Docetaxel administered on a weekly basis for metastatic breast cancer. J Clin Oncol 18(6):1212–1219PubMed
5.
Taxotere (docetaxel) injection concentrate. Full prescribing information 2013
6.
Rivera E, Mejia JA, Arun BK, Adinin RB, Walters RS, Brewster A, Broglio KR, Yin G, Esmaeli B, Hortobagyi GN, Valero V (2008) Phase 3 study comparing the use of docetaxel on an every-3-week versus weekly schedule in the treatment of metastatic breast cancer. Cancer 112(7):1455–1461. doi:10.​1002/​cncr.​23321 PubMedCrossRef
7.
Drummond DC, Meyer O, Hong K, Kirpotin DB, Papahadjopoulos D (1999) Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol Rev 51(4):691–743PubMed
8.
Immordino ML, Dosio F, Cattel L (2006) Stealth liposomes: review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomed 1(3):297–315CrossRef
9.
Klamerus KJ, Maloney K, Rudolph RL, Sisenwine SF, Jusko WJ, Chiang ST (1992) Introduction of a composite parameter to the pharmacokinetics of venlafaxine and its active O-desmethyl metabolite. J Clin Pharmacol 32(8):716–724PubMedCrossRef
10.
Gough K, Hutchison M, Keene O, Byrom B, Ellis S, Lacey L, McKellar J (1995) Assessment of dose proportionality: report from the statisticians in the pharmaceutical industry/pharmacokinetics UK joint working party. Drug Inf J 29:1039–1048
11.
Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, Bennett CL, Cantor SB, Crawford J, Cross SJ, Demetri G, Desch CE, Pizzo PA, Schiffer CA, Schwartzberg L, Somerfield MR, Somlo G, Wade JC, Wade JL, Winn RJ, Wozniak AJ, Wolff AC (2006) 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 24(19):3187–3205. doi:10.​1200/​jco.​2006.​06.​4451 PubMedCrossRef
12.
13.
Bruno R, Riva A, Hille D et al (1997) Pharmacokinetic and pharmacodynamic properties of docetaxel: results of phase I and phase II trials. Am J Health Syst Pharm 54(24 Suppl 2):S16–S19
14.
Hilkens PH, Verweij J, Stoter G, Vecht CJ, van Putten WL, van den Bent MJ (1996) Peripheral neurotoxicity induced by docetaxel. Neurology 46(1):104–108PubMedCrossRef
15.
Behar A, Pujade-Lauraine E, Maurel A, Brun MD, Chauvin FF, Feuilhade de Chauvin F, Oulid-Aissa D, Hille D (1997) The pathophysiological mechanism of fluid retention in advanced cancer patients treated with docetaxel, but not receiving corticosteroid comedication. Br J Clin Pharmacol 43(6):653–658PubMedCentralPubMedCrossRef
16.
Deeken JF, Slack R, Weiss GJ, Ramanathan RK, Pishvaian MJ, Hwang J, Lewandowski K, Subramaniam D, He AR, Cotarla I, Rahman A, Marshall JL (2013) A phase I study of liposomal-encapsulated docetaxel (LE-DT) in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol 71(3):627–633. doi:10.​1007/​s00280-012-2048-y PubMedCentralPubMedCrossRef
17.
Bruno R, Hille D, Riva A et al (1998) Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol 16(1):187–196PubMed
Metadata
Title
Phase I study of intravenously administered ATI-1123, a liposomal docetaxel formulation in patients with advanced solid tumors
Authors
Devalingam Mahalingam
John J. Nemunaitis
Laeeq Malik
John Sarantopoulos
Steven Weitman
Kamalesh Sankhala
Jessica Hart
Ahmed Kousba
Nicole S. Gallegos
Gavin Anderson
John Charles
Jon M. Rogers
Neil N. Senzer
Alain C. Mita
Publication date
01-12-2014
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2014
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-014-2602-x

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