Phase II Study of Weekly Docetaxel and Trastuzumab for Patients With HER-2–Overexpressing Metastatic Breast Cancer

Esteva, Francisco J.; Valero, Vicente; Booser, Daniel J.; Guerra, Laura; Murray, James L.; Pusztai, Lajos; Cristofanilli, Massimo; Arun, Banu K.; Esmaeli, Bita; Fritsche, Herbert A.; Sneige, Nour; Smith, Terry L.; Hortobágyi, Gabriel N.

doi:10.1200/jco.2002.07.058

Cited by 493 publications

(320 citation statements)

References 30 publications

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“…On the contrary, weekly docetaxel in combination with trastuzumab seems to be more toxic, with two independent studies reporting that approximately one quarter of cases were withdrawn because of severe toxicity [28,29].…”

Section: Discussionmentioning

confidence: 99%

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Gasparini

Gion²,

Mariani³

et al. 2006

Breast Cancer Res Treat

129

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Background A randomized Phase II study evaluated the activity of weekly paclitaxel versus its combination with trastuzumab for treatment of patients with advanced breast cancer overexpressing HER-2. Patients and methods Among 124 patients randomized, 123 are assessable for toxicity and 118 for response. Patients received weekly paclitaxel single agent (80 mg/m 2 ) or combined with trastuzumab (4 mg/kg loading dose, then weekly 2 mg/kg). HER-2 overexpression was determined by immunohistochemistry (IHC). Patients with 2+/3+ IHC scores were eligible. IHC was compared with HER-2 serum extracellular domain (ECD). Results Patient characteristics were similar in the two arms. Both treatments were feasible and well tolerated with no grade 4 hematologic toxicity. No patient developed cardiac toxicity. The combined treatment was statistically significant superior for overall response rate (ORR) (75% vs. 56.9%; P = 0.037), particularly in the subset of IHC 3+ patients (84.5% vs. 47.5%; P = 0.00050). A statistically significant better median time to progression was seen in the subgroup with IHC 3+ (369 vs. 272 days; P = 0.030) and visceral disease (301 vs. 183 days; P = 0.0080) treated with combination. Multivariable analysis of predictive factors showed that only IHC score retained statistically significant value for ORR (P = 0.0035). Conclusion Weekly paclitaxel plus trastuzumab is highly active and safe and it is superior to paclitaxel alone in patients with IHC score of 3+.

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Section: Discussionmentioning

confidence: 99%

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Gasparini

Gion²,

Mariani³

et al. 2006

Breast Cancer Res Treat

129

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“…In addition, the majority of patients who initially respond to Trastuzumab demonstrate disease progression within 1 year of treatment initiation. Combination of Trastuzumab with Paclitaxel (Seidman et al, 2001) or Docetaxel (Esteva et al, 2002) increase the response rate and overall survival.…”

Section: Naked Antibodiesmentioning

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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“…Although effective, the combination of doxorubicin-cyclophosphamide and trastuzumab resulted in a higher percentage of severe cardiac dysfunctions compared with paclitaxel and monoclonal antibody. This observation and results of preclinical studies led to the development of combinations of trastuzumab and other antiblastic drugs, such as cisplatin (Pegram et al, 1998), vinorelbine (Burstein et al, 2001), taxotere (Esteva et al, 2002), liposomal doxorubicin (Theodoulou et al, 2002) or weekly paclitaxel (Seidman et al, 2001). …”

mentioning

confidence: 99%

Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer

Gori¹,

Colozza²,

Mosconi³

et al. 2004

Br J Cancer

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Synergism between anti-HER2 monoclonal antibody (trastuzumab) and paclitaxel has been shown in vitro and in vivo. In previous experiences, weekly administration of trastuzumab and paclitaxel has shown significant activity in metastatic breast cancer. In this phase II study, we evaluated the activity and the toxicity of this weekly regimen in anthracycline-and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. Between November 1999 and July 2001, 25 patients were treated with trastuzumab (4 mg kg À1 i.v. loading dose followed by 2 mg kg À1 i.v. week À1 ) and paclitaxel (60 -90 mg m À2 h À1 i.v. infusion week À1 ). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, after 6 months of therapy, the decision to stop paclitaxel while continuing weekly trastuzumab was left to the physicians' judgement. At the median follow-up of 19.6 months (range 9.2 -38.1), all patients are evaluable for response and toxicity. We obtained four (16%) complete responses (CR), 10 (40%) partial responses (PR), four (16%) stable diseases and seven (28%) disease progressions. The response rate (CR þ PR) was 56% (95% CI, 36.5 -75.5%). The median duration of response was 10.4 months (range 4.1 -24.2 þ ). Median time to progression was 8.6 months (range 2.5 -24.2 þ ). The toxicity was mild; five patients experienced fever and chills during the first infusion of trastuzumab (20%); leukopenia grade 2 was recorded in one patient (4%). Two patients (8%) came off study for grade 3 cardiotoxicity (after 9 and 17 weeks of treatment, respectively): both had already received anthracyclines and taxanes. Onycholysis grade 2 was observed in five patients (20%). These results confirm that weekly administration of trastuzumab and paclitaxel is active in anthracycline-and taxane-pretreated metastatic breast cancer patients HER2-overexpressing. Since cardiac disfunctions grade 3 were observed (8%), we recommend that cardiac function should be monitored in these patients.

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Phase II Study of Weekly Docetaxel and Trastuzumab for Patients With HER-2–Overexpressing Metastatic Breast Cancer

Abstract: Weekly docetaxel and trastuzumab is an active combination for treating patients with HER-2-overexpressing metastatic breast cancer. Serum HER-2 ECD testing may be a promising method for monitoring patients on trastuzumab-based therapy.

Cited by 493 publications

References 30 publications

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Randomized Phase II Trial of weekly paclitaxel alone versus trastuzumab plus weekly paclitaxel as first-line therapy of patients with Her-2 positive advanced breast cancer

Novel antibodies as anticancer agents

Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer

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