Weekly paclitaxel plus trastuzumab in metastatic breast cancer pretreated with anthracyclines-a phase II multipractice study

John, Matthias; Hinke, Axel; Stauch, Martina; Wolf, H.; Mohr, Benno; Hindenburg, Hans-Joachim; Papke, Jens; Schlosser, Joachim

doi:10.1186/1471-2407-12-165

Cited by 14 publications

(16 citation statements)

References 25 publications

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“…In other prostate cancer phase I trials, OGX-011 was given prior to radical prostoctomy, while some “well tolerated” phase II trials were established based on the biologic effectiveness of OGX-011 [315]. …”

Section: Molecular Targeting Therapies and Apoptosismentioning

confidence: 99%

Apoptosis and Molecular Targeting Therapy in Cancer

Hassan

Watari

Abu-Almaaty

et al. 2014

BioMed Research International

943

720

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Apoptosis is the programmed cell death which maintains the healthy survival/death balance in metazoan cells. Defect in apoptosis can cause cancer or autoimmunity, while enhanced apoptosis may cause degenerative diseases. The apoptotic signals contribute into safeguarding the genomic integrity while defective apoptosis may promote carcinogenesis. The apoptotic signals are complicated and they are regulated at several levels. The signals of carcinogenesis modulate the central control points of the apoptotic pathways, including inhibitor of apoptosis (IAP) proteins and FLICE-inhibitory protein (c-FLIP). The tumor cells may use some of several molecular mechanisms to suppress apoptosis and acquire resistance to apoptotic agents, for example, by the expression of antiapoptotic proteins such as Bcl-2 or by the downregulation or mutation of proapoptotic proteins such as BAX. In this review, we provide the main regulatory molecules that govern the main basic mechanisms, extrinsic and intrinsic, of apoptosis in normal cells. We discuss how carcinogenesis could be developed via defective apoptotic pathways or their convergence. We listed some molecules which could be targeted to stimulate apoptosis in different cancers. Together, we briefly discuss the development of some promising cancer treatment strategies which target apoptotic inhibitors including Bcl-2 family proteins, IAPs, and c-FLIP for apoptosis induction.

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Section: Molecular Targeting Therapies and Apoptosismentioning

confidence: 99%

Apoptosis and Molecular Targeting Therapy in Cancer

Hassan

Watari

Abu-Almaaty

et al. 2014

BioMed Research International

943

720

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“…Treatment of human epithelial growth factor receptor 2 (HER2)-positive breast cancer, which accounts for 20–25% of all breast cancer patients, has rapidly evolved over the last decade [1, 2]. The clarification of the signaling pathway activated by HER2 and its impact on the formation of breast cancer, followed by the clinical development of effective HER2 targeted agents, have tremendously advanced the field of oncology.…”

Section: Introductionmentioning

confidence: 99%

Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States

Diaby

Adunlin

Ali

et al. 2016

Breast Cancer Res Treat

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Purpose Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC). Patients and Methods We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) was captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results. Results The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third line therapy. Conclusion Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50% reduction in the total drug acquisition cost for it to be considered a cost-effective strategy.

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“…Weekly, rather than the standard every-3-weeks, lower dosing of paclitaxel provides an efficacious method to deliver drug while maintaining a favorable toxicity profile. Various studies support weekly taxane dosing as an active regimen in MBC[6; 9; 11; 12; 13]. Importantly, this regimen is associated with a low incidence of severe hematologic toxicities and acute non-hematologic toxicities.…”

Section: Discussionmentioning

confidence: 99%

“…[6] Thus, it is believed that more frequent administrations of cytotoxic agents would be more effective in minimizing residual tumor burden compared to conventional dose-escalation chemotherapy[7; 9; 10]. Numerous mono and combination chemotherapy trials suggested that weekly administration of paclitaxel has a better therapeutic index than the standard every 3-week regimen and is not associated with increased side effects[9; 11; 12; 13]. These results are very encouraging for the incorporation of dose-dense chemotherapy in every day practice for breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Different administration strategies with paclitaxel induce distinct phenotypes of multidrug resistance in breast cancer cells

et al. 2013

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Both dose-dense and dose-escalation chemotherapy are administered in clinic. By approximately imitating the schedules of dose-dense and dose-escalation administration with paclitaxel, two novel multidrug resistant (MDR) cell lines Bads-200 and Bats-72 were successfully developed from drug-sensitive breast cancer cell line BCap37, respectively. Different from Bads-200, Bats-72 exhibited stable MDR and significantly enhanced migratory and invasive properties, indicating that they represented two different MDR phenotypes. Our results showed that distinct phenotypes of MDR could be induced by altered administration strategies with a same drug. Administrating paclitaxel in conventional dose-escalation schedule might induce recrudescent tumor cells with stable MDR and increased metastatic capacity.

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Weekly paclitaxel plus trastuzumab in metastatic breast cancer pretreated with anthracyclines-a phase II multipractice study

Cited by 14 publications

References 25 publications

Apoptosis and Molecular Targeting Therapy in Cancer

Apoptosis and Molecular Targeting Therapy in Cancer

Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States

Different administration strategies with paclitaxel induce distinct phenotypes of multidrug resistance in breast cancer cells

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