Posts Tagged ‘paclitaxel’

New Treatment for Her-2+ Metastatic Breast Cancer Opens at CORT

September 4, 2009

CORT has opened the Wyeth 3144A2 3005 WW Study testing the oral her-2 inhibitor, neratinib, in combination with paclitaxel (Taxol), versus standard therapy with trastuzumab (Herceptin) in combination with paclitaxel, for first-line treatment of her-2+ metastatic breast cancer. 

Neratinib is an oral anti-her-1/her-2 drug with demonstrated efficacy in metastatic her-2 positive breast cancer.  The safety studies have demonstrated acceptable and manageable toxicity of neratinib, including rash and occasional loose stools or diarrhea being most common.  As with other her-2 inhibiting drugs, neratinib may lower the cardiac ejection fraction, so serial monitoring of cardiac function is routine.  The Phase III study will compare the efficacy and tolerability of paclitaxel with either oral neratinib or trastuzumab (a monoclonal antibody against her-2 protein, given IV).

The potential advantages of neratinib include improved convenience (and possibly improved safety).  The drug is given orally.  

For more information about this study, visit our website at, or contact a Research Coordinator at 972-566-5588.  

Patients with her-2+ breast cancer may also be eligible for other studies and treatment at CORT, including non-study therapy.  The principle investigator at CORT is Dr. Barry Mirtsching.  He has personally conducted over 200 trials in cancer therapy over 16 years, many in breast cancer management.  Experience in both trial and non-trial breast cancer management benefits patients by producing better treatment outcomes.  Care at CORT is individual and personal, with adequate time for problem-solving and direct contact with the physician.

Who Benefits from Taxanes: Controversy in Breast Cancer Management

October 13, 2007

The benefit of adjuvant paclitaxel (Taxol), in addition to anthracycline-based chemotherapy was evaluated in the CALGB 9344 study, which has previously been reported.  CALGB 9344 evaluated 4 cycles of escalating doses of doxorubicin (Adriamycin) combined with a fixed dose of cyclophosphamide (AC) with or without 4 cycles of sequential Taxol in 3170 women with node-positive primary breast cancer. After 52 months of follow-up, important changes were noted when compared with earlier interim analyses at 21 and 30 months follow-up.  Specifically, the addition of sequential paclitaxel to AC significantly improved the disease-free survival (P = .0324), but not overall survival (P = .0745). The disease-free survival rates for patients treated with sequential AC and Taxol versus those treated with AC alone at 48 months follow-up were 73% vs 70%, respectively. Overall survival rates for the 2 groups at 48 months were 84% vs 81%, respectively.

Molecular subtypes of breast cancer are now better defined.  Her-2 positive breast cancer (about 15% of all breast cancer) is an aggressive subtype, with growth driven by the over-expression of her-2 growth regulating receptors on the cancer cells.  Older studies, such as CALGB 9344 did not include the use of adjuvant anti-her-2 treatment, trastuzumab (Herceptin), in addition to chemotherapy, which is now the standard-of-care for her-2 positive disease.  It has been hypothesized that her-2 positive cancers benefit more from chemotherapy than other cancers, possibly because of increased levels of intracellular topoisomerase II (topo II), or because of a higher proliferation rate.  The question of whether her-2 positive breast cancer patients (when compared to her-2 negative patients) benefit to a greater degree by the addition of Taxol to AC was analyzed in a retrospective analysis of the CALGB 9344 study, which was published in the New England Journal of Medicine, October 11, 2007. 

In this analysis, Her-2 positivity was associated with a significant benefit from paclitaxel. The interaction between Her-2 positivity and the addition of Taxol to the treatment was associated with a hazard ratio for recurrence of 0.59 (P=0.01), a 41% reduction in risk. Patients with a Her-2-positive breast cancer benefited from paclitaxel, regardless of estrogen-receptor status.  Taxol did not benefit patients with HER2-negative, estrogen-receptor–positive cancers.   However, Her-2 negative, estrogen-receptor negative patients did have a significant reduction in the hazard ratio for recurrence (P=0.002), indicating that Taxol has benefit for some patients who are not Her-2 positive. 

Oncologists have been cautioned about premature interpretation and possible clinical practice changes until further study can confirm these results.  The CALGB analysis was retrospective, and the aggregate results of the study did show general benefit of Taxol adjuvant therapy for breast cancer patients.  Similar findings of benefit have been reported for adjuvant use of docetaxel (Taxotere) for adjuvant treatment of node-positive patients.  In addition, the use of taxol in the CALGB study (every 3 weeks) was not optimal, based on more recent studies that have demonstrated that Taxol is more effective when given on a more frequent schedule (weekly).  Therefore, the conclusion that adjuvant addition of weekly Taxol to AC might not be beneficial to estrogen-receptor positive patients requires confirmation.  Newer taxanes have been developed (for example, Abraxane, a nanoparticle of taxol in albumin protein), which may be more effective that Taxol.  A US Oncology study suggests that a more intensive taxane therapy and schedule may be a significant addition for her-2 negative and estrogen-receptor negative patients. Further study of taxanes in all molecularly-defined groups of patients is warranted, to determine what the degrees of benefits may be.  Finally, the substitution of taxane therapy for anthracycline-based treatment in the adjuvant setting appears to be a promising strategy in reducing possible cardiac toxicity of treatment. 

In summary, the CALGB study analysis is provacative, but not unexpected. Not all patients derive the same benefit from adjuvant treatments with different agents.  Taxane therapy should not be an immediate addition to every patient, but it should be considered based on a careful and individualized basis of each patient’s breast tumor characteristics, stage, and recurrence risk.  Additional study of taxane treatment in clinical trials, such as those offered at CORT, will be important in helping to improve treatment selection for patients.  In the meantime, it is premature to routinely deny patients with estrogen-receptor positive cancers the addition of a taxane in adjuvant therapy, without additional confirmatory study.

Chemotherapy and Sorafenib (Nexavar) for First-Line Treatment of Metastatic Melanoma

September 29, 2007

The combination of carboplatin (Paraplatin) and paclitaxel (Taxol) is active in metastatic melanoma. This combination of drugs is not approved for melanoma treatment, but is approved and commonly utilized in treatment of lung and other cancers. Treatment with Paraplatin and Taxol has manageable risks, which include fatigue, hair loss, nausea, vomiting, low blood counts, fever, infection, sensory neuropathy, and allergic reactions.

Sorafenib (Nexavar) is an oral drug that targets several specific growth promoting proteins in cancer cells. It inhibits b-raf (increased in melanoma cells) and it blocks angiogenesis (blood vessel formation). It is FDA-approved in the treatment of metastatic renal (kidney) cancer. The risks of Nexavar include fatigue, nausea, vomiting, diarrhea, rash, proteinuria (protein in the urine), increased blood pressure, low thyroid function, low blood counts, delayed wound healing, bleeding and thrombosis.

CORT is testing the combination of Paraplatin and Taxol with or without Nexavar in the first-line treatment of metastatic melanoma.

For more information on these studies, visit, or speak with a Study Coordinator at 972-566-5588.

Sunitinib (Sutent) in Metastatic Breast Cancer and Triple-Negative (ER-,PR-, and Her-2-negative) Breast Cancer

September 27, 2007

Breast cancers that do not contain growth regulator proteins for estrogen receptor (ER), progesterone receptor (PR), or HER-2 are termed “triple negative” tumors. Triple negative tumors are aggressive. Patients with metastatic triple negative tumors have a poor prognosis when treated with standard therapies.Sutent® (sunitinib) is an oral targeted drug that blocks growth promoting receptors PDGF-R and VEGF-R. It blocks angiogenesis, the process of new blood vessel growth in tumors. Without new blood vessel formation, tumor growth is inhibited.The risks of Sutent are hypertension, abdominal pain, slow wound healing, changes in blood chemistry or blood counts, reduced thyroid function, and bleeding. Rare cases of reduced heart function or brain white matter injury have occurred.

CORT is conducting a study to evaluate the addition of Sutent versus standard chemotherapy in patients with triple negative metastatic breast cancer. Several standard treatments are allowed in this study, and the physician may choose the one felt most appropriate for the individual patient. The study will determine is Sutent has comparable or superior activity to standard treatments in this high risk group of patients.Anti-angiogenic treatment added to standard chemotherapy for metastatic breast cancer has already been shown to increase disease response to treatment and prolong disease control.

CORT is conducting a study of study comparing standard therapy with two drugs, bevacizumab (Avastin) and paclitaxel (Taxol) to the combination of Sutent and Taxol. Avastin is an antibody that blocks angiogenesis, with risks similar to those of Sutent. Avastin requires intravenous administration, and occasional infusion reactions (allergic reactions) do occur. The study will determine is Sutent is comparable or superior to Avastin, when either is combined Taxol with chemotherapy.

For more information about these studies, visit or contact a Research Coordinator at 972-566-5588.

Lapatinib (Tykerb) for Treatment of Metastatic Breast Cancer

September 27, 2007

According to results recently presented at the 2007 annual meeting of the American Society of Clinical Oncology, the targeted agent Tykerb® (lapatinib) may be effective in shrinking cancer that has spread to the brain among some patients with breast cancer.Tykerb is a targeted therapy that has produced promising results in women with metastatic or refractory breast cancer. Targeted therapies are anticancer drugs that are designed to treat cancer cells while reducing damage to normal, healthy cells. Tykerb targets two proteins that often function abnormally in breast cancer cells—HER2 and EGFR. When these proteins are increased in cancer cells (a condition referred to as HER2-positive and/or EGFR-positive cancers), the proteins tend to function abnormally, resulting in uncontrolled, faster growth of cancerous cells. Tykerb decreases or prevents the growth of these cancerous cells.Researchers recently reported results from a clinical study that suggested Tykerb may have anticancer activity among patients with brain metastasis from advanced HER2-positive breast cancer. This study included 241 patients whose brain metastasis continued to progress following therapy with Herceptin® (trastuzumab) and radiation therapy.Nearly half of the patients (46%) experienced at least a 20% reduction in the size of their brain metastasis.An additional 42% of patients achieved stabilization of their disease for at least eight weeks.Overall, 22% of patients had no signs of disease progression within the first six months of treatment with Tykerb.

The most common severe side effects were diarrhea, skin rash, nausea, vomiting, and fatigue.

The researchers concluded that among patients with advanced breast cancer: “Tykerb has promise in the treatment of brain metastases.” Further study of Tykerb in advanced breast cancer is ongoing at CORT. We are conducting a trial of Tykerb with either capecitabine (Xeloda) or topotecan (Hycamptin) chemotherapy for treatment of patients whose brain metastases continue to progress following treatment with Herceptin and radiation therapy.

Tykerb may also increase the activity of other therapies used for HER2-positive metastatic breast cancer patients. Currently, the combination of Herceptin and Taxol (paclitaxel) is a standard-of-care for initial therapy in these patients. CORT is conducting a study that compares that standard treatment of Herceptin and Taxol with or without the addition of Tykerb.

For more information about these studies, visit or contact a Research Coordinator at 972-566-5588.

Lung Cancer Survival Improved by Cetuximab (Erbitux)

September 22, 2007

ImClone and Bristol Myers Squibb (BMS) released a press announcement on 9/12/07 that cetuximab (Erbitux), a monoclonal anti-epidermal growth factor receptor (EGFR) antibody, improved survival of advanced non-small cell lung cancer (NSCLC) patients when combined with standard chemotherapy when compared to standard chemotherapy alone. Data from the FLEX study have not been made public, but release is anticipated, based on the positive release of the announcement.Cetuximab is already an approved therapy in treatment of metastatic colon cancer and head & neck cancer.Cetuximab has been under study at CORT since 1999. It is well-tolerated, with rash and diarrhea as common side effects. Infusion reactions, and more rarely, drug-induced interstitial pneumonia may occur. Cetuximab is not yet approved in the treatment of NSCLC.Bevacizumab (Avastin), a monoclonal anti-vascular endothelial growth factor (VEFG) antibody, has also been shown to improve survival in advanced NSCLC, when combined with chemotherapy. Bevacizumab may cause increases in blood pressure, proteinuria, bleeding or thrombosis, slow wound healing, and uncommon infusion reactions. Rare cases of bowel perforation have occurred.

CORT is conducting a first-line trial of cetuximab and bevacizumab in NSCLC as part of a multicenter study. The study compares standard chemotherapy with carboplatin and paclitaxel to either cetuximab and bevacizumab alone, or the combination of both antibodies with carboplatin and paclitaxel.  For more information on this study, visit, or speak with a Researh Coordinator at 972-566-5588.