Randomized Phase II Study of BR96-Doxorubicin Conjugate in Patients With Metastatic Breast Cancer

Tolcher, Anthony W.; Sugarman, Steven; Gelmon, Karen A.; Cohen, Roger; Saleh, Mansoor N.; Isaacs, Claudine; Young, Leslie; Healey, Diane; Onetto, Nicole; Slichenmyer, William J.

doi:10.1200/jco.1999.17.2.478

Cited by 241 publications

(117 citation statements)

References 3 publications

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“…In phase I and II clinical trials of this conjugate, patients with metastatic breast cancer experienced a marked decrease in side effects, in comparison with unconjugated doxorubicin administration. However, unconjugated doxorubicin showed increased potent antitumor activity (Tolcher et al, 1999;Saleh et al, 2000).…”

Section: Immunotoxinsmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

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In recent years antibodies, whether generated by traditional hybridoma technology or by recombinant DNA strategies, have evolved from Paul Ehrlich's 'magic bullets' to a modern age 'guided missile'. In the recent years of immunologic research, we are witnessing development in the fields of antigen screening and protein engineering in order to create specific anticancer remedies. The developments in the field of recombinant DNA, protein engineering and cancer biology have let us gain insight into many cancer-related mechanisms. Moreover, novel techniques have facilitated tools allowing unique distinction between malignantly transformed cells, and regular ones. This understanding has paved the way for the rational design of a new age of pharmaceuticals: monoclonal antibodies and their fragments. Antibodies can select antigens on both a specific and a high-affinity account, and further implementation of these qualities is used to target cancer cells by specifically identifying exogenous antigens of cancer cell populations. The structure of the antibody provides plasticity resonating from its functional sites. This review will screen some of the many novel antibodies and antibody-based approaches that are being currently developed for clinical applications as the new generation of anticancer agents.

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Section: Immunotoxinsmentioning

confidence: 99%

Novel antibodies as anticancer agents

2007

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“…ont été décrits et certains ont été évalués chez l'homme, malheureusement sans succès. À titre d'exemple, on peut citer un essai clinique de phase II dans le cancer du sein métastatique avec un immunoconjugué BR96-doxorubicine ciblant l'antigène Le y ; il démontra un manque d'efficacité du conjugué par rapport à la doxorubicine seule et une forte toxicité gastro-intestinale due à l'expression de l'antigène Le y par certains tissus sains [3]. Les échecs de ces immunoconjugués de première génération étaient principalement liés à l'instabilité du conjugué, à l'absence de libération de la drogue dans la cellule ou à la libération d'une forme inactive, ainsi qu'à la faible efficacité des agents cytostatiques utilisés nécessitant le couplage d'un nombre trop important de molécules par anticorps.…”

Section: Jean-françois Haeuw Véronique Caussanel Alain Beckunclassified

Les immunoconjugués, anticorps « armés » pour combattre le cancer

2009

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“…14,[27][28][29][30] Significant preclinical in vivo activity was also seen in models of breast cancer, pancreatic cancer, and melanoma. [31][32][33][34][35][36][37][38] E7974 thus offers significant promise of activity in taxane-resistant tumor types, regardless of whether the mechanism driving resistance is based on P-glycoprotein or tubulin mutations. 39 In the toxicology studies, E7974 was examined after single intravenous (IV) administration in mice, rats (1, 3, or 6 mg/kg), and dogs (0.1 or 0.23 mg/kg).…”

Section: Introductionmentioning

confidence: 99%

A phase 1 trial of E7974 administered on day 1 of a 21‐day cycle in patients with advanced solid tumors

Rocha-Lima

Bayraktar

MacIntyre

et al. 2012

Cancer

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BACKGROUND: E7974, a synthetic analog of hemiasterlin, interacts with the tubulin molecule and overcomes resistance to other antitubulin drugs (taxanes and vinca alkaloids). METHODS: In a phase 1 study, E7974 was given intravenously over a 2-to 5-minute infusion on day 1 of every 21-day cycle. Adult patients with advanced refractory solid tumors who had adequate organ function and Eastern Cooperative Oncology Group performance status 0 to 2 were eligible for this study. A modified Fibonacci schema was used. The maximal tolerated dose (MTD) was the dose where <2 of 6 patients developed a dose-limiting toxicity (DLT). RESULTS: Twentyeight patients (19 men and 9 women; median age, 64 years) treated at different cohort dose levels (0.18 mg/m 2 , 0.27 mg/m 2 , 0.36 mg/m 2 , 0.45 mg/m 2 , and 0.56 mg/m 2 ) received a total of 66 courses of E7974. The MTD was established at 0.45 mg/m 2 , where 1 of 6 patients experienced DLT (grade 4 febrile neutropenia). Of the 17 refractory colon cancer patients with a median of 3 prior treatments, stable disease was seen in 7 patients (41%). There were no tumor responses. Median progression-free survival was 1.2 months, and median overall survival was 6.7 months. In pharmacokinetic analysis, E7974 was characterized by a fast and moderately large distribution (37.95-147.93 L), slow clearance (2.23-7.15 L/h), and moderate to slow elimination (time to half-life, 10.4-30.5 hours). CONCLUSIONS: This study shows that E7974 once every 21-day cycle shows antitumor activity in patients with refractory solid tumors. The recommended phase 2 dose is 0.45 mg/m 2 .

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Randomized Phase II Study of BR96-Doxorubicin Conjugate in Patients With Metastatic Breast Cancer

Cited by 241 publications

References 3 publications

Novel antibodies as anticancer agents

Novel antibodies as anticancer agents

Les immunoconjugués, anticorps « armés » pour combattre le cancer

A phase 1 trial of E7974 administered on day 1 of a 21‐day cycle in patients with advanced solid tumors

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