Capecitabine combination therapy reduces early breast cancer recurrence...

Capecitabine, is an orally-administered chemo therapeutic agent used in the treatment of metastatic breast and colorectal cancers.

Mode of action :

Capecitabine is a prodrug, that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue. The activation of capecitabine follows a pathway with three enzymatic steps and two intermediary metabolites, 5'-deoxy-5-fluorocytidine (5'-DFCR) and 5'-deoxy-5-fluorouridine (5'-DFUR), to form 5-fluorouracil. Its being used (& FDA approved) in the treatment of adjuvant in colorectal cancer, metastatic colorectal cancer and Metastatic breast cancer - used in combination with docetaxel, after failure of anthracycline-based treatment. Also as monotherapy, if the patient has failed paclitaxel-based treatment, and if anthracycline-based treatment has either failed or cannot be continued for other reasons.

Recently, Finnish Breast Cancer Group and published in The Lancet Oncology shows women at intermediate to high-risk of early breast cancer recurrence who received capecitabine as part of their chemotherapy regimen had a 34% reduction in the risk of the disease returning or death, compared with those taking the chemotherapy combination regimen without capecitabin. The pre-planned three-year interim analysis of a randomised, prospective trial compared adjuvant capecitabine in combination with docetaxel and cyclophosphamide plus epirubicin for the treatment of early breast cancer with the standard, non-capecitabine regimen (docetaxel, epirubicin, cyclophosphamide and fluorouracil). The analysis also found that patients taking the capecitabine-containing regimen were significantly less likely to have their cancer spread (distant metastasis) to another part of the body (a 36% reduction in risk was observed). This is the first phase III randomised trial to report efficacy of capecitabine combination therapy in the adjuvant treatment of early breast cancer.

Though capecitabine, has already been shown to be effective in patients with advanced breast cancer, but the most important conclusion the researchers have arrived is "capecitabine-containing regimen in the early stages of breast cancer may offer survival benefits for women".....

Source :http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2809%2970307-9/fulltext

New small molecule inhibitor could be a safe and first-line treatment for metastatic breast cancer

Mesupron® (see structure below) is a new small molecule inhibitor, taken as a pill, that inhibits the uPA system. The results from a recent phase II clinical study suggest that the drug could be a safe and first-line treatment that extends progression-free survival for metastatic breast cancer patients, when combined with the chemotherapeutic drug Capecitabine.

The study included 132 patients with metastatic breast cancer from 20 centers in five countries. In the trial, patients who took Mesupron combined with Capecitabine went without the return of disease for a median 8.3 months after the therapy. Patients who only took Capecitabine had a progression-free survival of 7.5 months.

"The combination of oral agents was convenient for and well tolerated by the patients," says Goldstein. "Plans for future studies are ongoing."

The drug was developed by WILEX, a German pharmaceutical company that focuses on the development of small molecule inhibitors and other new targeted cancer drugs designed to give patients treatment options with fewer side effects than traditional chemotherapy. In the Phase II study, Goldstein and her collaborators also investigated the safety and efficacy of the drug, as well as the objective response rate  the patient population who had no sign of disease after a specific amount of time.

Nine percent of the patients who received only Capecitabine had a complete objective response after 24 weeks. The objective response rate among the patients taking the combination therapy was nearly twice that, at 17 percent. The researchers also looked at different subgroups of participants to try to identify which patients might receive the most benefit from a combination therapy involving Mesupron. Among 109 Caucasian patients, the progression free survival was 7.5 months for patients who received Capecitabine alone, and 9.1 months for those who also received Mesupron.

The drug also showed a significant improvement for patients who had previously received treatment  before their disease became metastatic. In the subgroup of patients (n=95) who received adjuvant chemotherapy following the primary diagnosis of breast cancer, progression free survival improved from 4.3 months in the Capecitabine alone group to 8.3 months in the Mesupron combination group.....

Ref : http://www.fccc.edu/information/news/press-releases/2012/2012-12-07-SABC-Goldstein-WILEX.html

New small molecule inhibitor could be a safe and first-line treatment for metastatic breast cancer

Capecitabine increases disease-free survival for HER2-negative breast cancer patients

Treatment with the chemotherapy agent capecitabine increased disease-free survival for women with HER2-negative breast cancer that was not eliminated by presurgery chemotherapy, according to results from the phase III CREATE-X clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8-12.

Treatment given to shrink or eliminate a tumor before surgery is called neoadjuvant therapy. In some patients with breast cancer treated with neoadjuvant chemotherapy, residual invasive cancer can be detected in breast tissue samples and lymph nodes removed during surgery. These patients tend to have worse long-term outcomes compared with women who respond completely to neoadjuvant therapy.

"It has been suggested that patients with residual invasive disease after neoadjuvant chemotherapy have chemoresistant breast cancer, but there have been no large-scale clinical trials to test whether adjuvant systemic chemotherapy is beneficial for these patients," said Masakazu Toi, MD, PhD, a professor at Kyoto University Hospital in Japan, and founder and senior director of the Japan Breast Cancer Research Group (JBCRG). "CREATE-X was designed to evaluate this clinical question by testing whether capecitabine could improve disease-free survival for patients with residual invasive disease after neoadjuvant chemotherapy.

Capecitabine increases disease-free survival for HER2-negative breast cancer patients

Specific sequence of drugs reduces cost of treating metastatic breast cancer while preserving quality of life

The researchers developed three different computer models to predict how a hypothetical set of 10,000 patients with specific types of metastatic breast cancer would respond to different sequences and types of chemotherapy. For this study, the patient's cancer was either no longer responding to hormone therapies (endocrine resistant) or was a type of the disease called triple-negative breast cancer.

Currently, there are many chemotherapy choices to treat metastatic breast cancer. Oncologists have some preferences of which drugs to use early in treatment, but there is little clear evidence on the best order in which to give the drugs. The researchers consulted oncologists and experts in the field to choose which chemotherapy drugs were preferred choices to include in the study.

Mimicking clinical practice, and based upon existing data, the researchers then assumed that if a person started treatment with one drug, they would change to a second-choice treatment after their cancer stopped responding to the first drug, or if the side effects weren't tolerable. The purpose of the study was to test whether putting the drugs in one sequence compared to another could keep the patient on treatment for similar times while decreasing their side effect and/or cost burden.

"The cost of cancer drugs in the U.S. has rapidly increased, even for generics. As a society, we urgently need more strategies to reduce cancer drug costs without compromising outcomes, and our analysis provides quantifiable evidence to help providers choose lower priced, but equally effective sequences of drugs," said Stephanie B. Wheeler, PhD, MPH, professor of health policy & management at UNC Gillings and associate director of community outreach and engagement at UNC Lineberger and corresponding author of the article. "More spending on cancer care does not necessarily confer greater health benefits."

The costs calculated in this study were inclusive of medical and nonmedical costs borne by patients, including lost productivity. In this simulation, after two years, nearly all women would have completed the first three sets of treatment, but the cancer would cause the death of about one-third of the women. Productivity days lost due to sickness were similar across chemotherapy sequences, so most of the cost difference was due to drug savings. In the simulation, patients were placed in three groups, depending on what treatments they had already received for earlier episodes of breast cancer.

Outcomes in the three groups were:

• For people who had not previously received the common chemotherapy drug categories, including a taxane (e.g., paclitaxel) or an anthracycline (e.g., capecitabine), treatment with paclitaxel then capecitabine followed by doxorubicin corresponded to the highest expected gains in quality of life and lowest costs.
• For people who had previously received a taxane and an anthracycline drug, treatment with carboplatin, followed by capecitabine, followed by eribulin, corresponded to the highest expected gains in quality of life and lowest costs.
• For people who had previously received a taxane but not an anthracycline, treatment sequences beginning with capecitabine or doxorubicin, followed by eribulin, were most cost-effective.

"The drugs we studied are already recommended and reimbursed for the treatment of metastatic breast cancer, but the optimal sequencing of them has been unclear, which has led to considerable variation in physician preference and practice. Our study suggests that treatment sequencing approaches that minimize costs early may improve the value of care," Wheeler said. "The implications of this study are fairly straightforward for medical oncologists and those developing value-based clinical pathways to implement in practice now."

UNC Lineberger's Katherine E. Reeder-Hayes, MD, MBA, MSc, section chief of breast oncology and associate professor of medicine at UNC School of Medicine and one of the study's authors, said the treatment choices for metastatic breast cancer are constantly changing, and new options for targeted therapy have emerged even since this study was conducted. "Many oncologists and patients find that there aren't any more targeted therapies that fit the cancer's molecular profiles, so they are left with the choice of a number of chemotherapy drugs that may feel pretty similar or have an unclear balance of pros and cons.

"In that scenario, I hope our study will help expand the framework that we use to make these decisions from one where we just think about the biologic action of the drug to one where we also consider the bigger picture of what the treatment experience is like for the patient, including their financial burden, investment of time, and side effects," Reeder-Hayes added. "The most potent drug isn't always the next best choice depending on what the patient values and wants to accomplish with their treatment."

Looking ahead, the researchers have developed a financial navigation program to further support patients in managing the out-of-pocket costs of their cancer care. This program has been effective and well received by patients, caregivers and providers. The team is currently scaling up the intervention in nine rural and non-rural oncology practices across North Carolina to understand how well it works in different care settings. Cancer patients who need financial support managing the cost of their cancer care are being recruited for this undertaking.

Ref : https://ascopubs.org/doi/10.1200/JCO.21.02473

FDA approves Vistogard (uridine triacetate) for emergency treatment of chemotherapy overdose

The U.S. Food and Drug Administration today approved Vistogard (uridine triacetate) for the emergency treatment of adults and children  who receive an overdose of the cancer treatment fluorouracil or  capecitabine, or who develop certain severe or life-threatening 
toxicities within four days of receiving these cancer treatments.

 "Treating cancer requires not only selecting which drug may be most  effective and well tolerated, but ensuring the correct dose is given at  proper intervals. While rare, unintentional overdose can occur," said  Richard Pazdur, M.D., director of the Office of Hematology and Oncology  Products in the FDA's Center for Drug Evaluation and Research. "Today's  approval is a first-of-its-kind therapy that can potentially save lives following overdose or life-threatening toxicity from these chemotherapy agents."

 Fluorouracil (taken by infusion) and capecitabine (taken orally) are similar types of chemotherapy that have been used for decades to treat several types of cancer, including breast and gastrointestinal cancers. An overdose of fluorouracil or capecitabine is rare, but when it occurs,the effects are serious and can be fatal.

  

Vistogard, taken orally, blocks cell damage and cell death caused by fluorouracil chemotherapy. Patients should take Vistogard as soon as  possible after the overdose (whether or not they have symptoms) or early-onset (within four days) of severe or life-threatening toxicity. The patient's health care provider will determine when he or she should 
return to the prescribed chemotherapy after treatment with Vistogard.

  

The efficacy and safety of Vistogard were studied in 135 adult and pediatric cancer patients who were treated in two separate trials and had either received an overdose of flourouracil or capecitabine, or had early-onset, unusually severe or life-threatening toxicities within 96 
hours after receiving flourouracil (not due to an overdose). The studies' primary measure was survival at 30 days or until chemotherapy  could resume if prior to 30 days. Of those who were treated with  Vistogard for overdose, 97 percent were still alive at 30 days. Of those treated with Vistogard for early-onset severe or life-threatening toxicity, 89 percent were alive at 30 days. In both studies, 33 percent of patients resumed chemotherapy in less than 30 days.

FDA approves Vistogard (uridine triacetate) for emergency treatment of chemotherapy overdose

Eribulin effective in metastatic breast cancer, researchers find

An  international research team, led by Dartmouth's Peter A. Kaufman, MD, published findings in the Journal of Clinical Oncologydemonstrating that, while not superior to capecitabine, eribulin is an active and well-tolerated therapy in women with metastatic breast cancer (MBC) receiving this therapy as a first, second, or third line chemotherapy regimen. Additionally, these patients had all been previously treated with both an anthracycline and a taxane in either the adjuvant or metastatic setting. This study is the first to address the use of eribulin early in the course of metastatic breast cancer, specifically either the first or second line setting

 

"Additionally, it is of great interest that subset analysis suggests that eribulin may be particularly active and effective in triple negative MBC, which is known to be an aggressive subset of breast cancer, and one associated unfortunately with a particularly poor prognosis overall," said Kaufman.

Eribulin has been approved in numerous countries in the third line or latter setting for the treatment of MBC, and is increasingly widely used. It is the only chemotherapeutic agent shown to have a survival benefit for patients with MBC in the third line or latter chemotherapeutic setting. Given previous research findings, and now findings from this large international trial, there has been great interest from oncologists and other clinicians in the potential impact that eribulin might have earlier in the course of MBC.

This phase III randomized trial assigned 1,099 women who had previously been treated with an anthracycline or a taxane to either eribulin or capecitabine as their first, second, or third line chemotherapy for advanced MBC. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary endpoints were overall survival and progression-free survival.

"While there is not a statistically significant difference in overall survival with eribulin in comparison to capecitabine, the median overall survival seen with eribulin is in fact numerically slightly superior to that of capecitabine," explained Kaufman.

Ref : http://jco.ascopubs.org/content/early/2015/01/20/JCO.2013.52.4892

Eribulin effective in metastatic breast cancer, researchers find  

Drug combination lengthens lives of metastatic colorectal cancer patients

                         fluoropyrimidine                    TAS-102

 Capecitabine

A drug developed 50 years ago and abandoned because it was considered to be too toxic has gained a second life in an international clinical trial. Research led by scientists at Dana-Farber Cancer Institute showed the drug and a potentiating agent lengthened the lives of patients with metastatic colorectal cancer, all of whom had exhausted available standard treatments.

In a paper published online today by the New England Journal of Medicine, investigators at Dana-Farber and research centers around the world found that the drug combination - given as a single pill known as TAS-102 - not only extended patients' overall survival, but also delayed the advance of the disease and did so with very few side effects.

According to the study authors, the results are especially impressive because half of the patients had just finished treatment with the standard class of chemotherapy agents - fluoropyrimidines (e.g. 5-fluorouracil [5-FU] or capecitabine [Xeloda]) but had failed to benefit from them. The fact that TAS-102 temporarily halted the disease in many of these patients suggests that it operates through a different biochemical pathway than 5-FU, and therefore may serve as an alternative to standard therapy.

"Colorectal cancer is the second most common cause of cancer deaths [after lung cancer] in the United States and is an enormous health problem around the world," said the study's lead author, Robert J. Mayer, MD, faculty vice president for academic affairs, medical oncologist and colorectal cancer researcher at Dana-Farber. "To have a well-tolerated, effective new drug in a cancer that is so prevalent is good news for patients."

The trial, a phase 3 study involving major cancer research institutions in Europe, the United States, Australia and Japan, enrolled 800 patients with metastatic colorectal cancer that was progressing despite previous treatment. Participants were randomly assigned to receive TAS-102 or a placebo pill...

More : http://www.nejm.org/doi/full/10.1056/NEJMoa1414325

Drug combination lengthens lives of metastatic colorectal cancer patients

Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study

In continuation of my updates on Erlotinib, gemcitabine and capecitabine

Additional treatments for locally advanced pancreatic cancer don't appear to boost survival, a new French study reports.

Researchers looked at the effects of adding a second drug -- erlotinib (Tarceva) -- to the initial round of chemotherapy. They also tested whether adding radiation to a second round of chemotherapy (chemoradiotherapy) would offer any survival benefit.

 erlotinib (Tarceva)

Unfortunately, the addition of the second drug didn't help people live longer, and those on chemoradiotherapy didn't fare any better.

"Chemoradiotherapy was not superior to chemotherapy," said the study's senior author, Dr. Pascal Hammel. Hammel is from the department of gastroenterology-pancreatology at Beaujon Hospital, in Clichy, France.

The study was funded by the pharmaceutical company Roche, the maker of Tarceva, and the French National Institute of Cancer.

More than 53,000 Americans are diagnosed with pancreatic cancer annually, the U.S. National Cancer Institute (NCI) says. About 42,000 Americans die each year from the disease, the NCI reports.

The new study focused on 449 people with pancreatic cancer. Their average age was just over 63.

All received standard four-month chemotherapy with the drug gemcitabine (Gemzar). Gemzar is currently used to treat a range of cancers, including pancreatic, ovarian, breast, and non-small cell lung cancers, the drug's labeling information says. For the study, about half the patients (219) also took Tarceva along with Gemzar.

 gemcitabine (Gemzar).

After completing initial treatment, imaging tests revealed that 269 patients appeared to have tumors that were under control. That meant their cancer was stable and didn't appear to have spread, or metastasized.

But the tumors couldn't be surgically removed because they had developed around the arteries surrounding the pancreas, study authors said.

About half this group of stable patients (136) received two additional months of the same chemotherapy regimen. The other half (133) was treated with a combination of radiation and the chemotherapy drug capecitabine (Xeloda).

 capecitabine (Xeloda)

After three years of follow-up, the researchers found that patients given Gemzar chemotherapy alone survived an average of 13.6 months. Those given the combination of Gemzar and Tarceva had an average survival of 11.9 months, the study found.

Patients treated with chemoradiotherapy lived an average of 15.2 months. Those who got chemotherapy alone lived an average of 16.5 months, the study found.

Hammel said there's still work to be done to improve the results of both chemotherapy and radiotherapy treatments.

But for now, Dr. Deborah Schrag agreed that "the French trial demonstrates that routine addition of chemo-radiation following initial chemotherapy for patients with locally advanced pancreatic cancer does not improve survival compared to continued chemotherapy." Schrag, chief of the Division of Population Sciences, Medical Oncology, at the Dana-Farber Cancer Institute in Boston, wrote an accompanying editorial in the same issue of the journal.

"[And] given the burdens of daily radiation therapy, there is no routine role for the application of this treatment strategy," added Schrag.

Schrag said it's possible there might be a certain group of pancreatic cancer patients who could get some measurable benefit from radiation. "Further evaluation of the tumor samples from the study participants might help to more precisely determine who might benefit from radiation, and such data are eagerly awaited," she said.

Additional Treatments Offer Little Benefit for Pancreatic Cancer: Study  

Drug combination lengthens lives of metastatic colorectal cancer patients

                         fluoropyrimidine                    TAS-102

 Capecitabine

A drug developed 50 years ago and abandoned because it was considered to be too toxic has gained a second life in an international clinical trial. Research led by scientists at Dana-Farber Cancer Institute showed the drug and a potentiating agent lengthened the lives of patients with metastatic colorectal cancer, all of whom had exhausted available standard treatments.

In a paper published online today by the New England Journal of Medicine, investigators at Dana-Farber and research centers around the world found that the drug combination - given as a single pill known as TAS-102 - not only extended patients' overall survival, but also delayed the advance of the disease and did so with very few side effects.

According to the study authors, the results are especially impressive because half of the patients had just finished treatment with the standard class of chemotherapy agents - fluoropyrimidines (e.g. 5-fluorouracil [5-FU] or capecitabine [Xeloda]) but had failed to benefit from them. The fact that TAS-102 temporarily halted the disease in many of these patients suggests that it operates through a different biochemical pathway than 5-FU, and therefore may serve as an alternative to standard therapy.

"Colorectal cancer is the second most common cause of cancer deaths [after lung cancer] in the United States and is an enormous health problem around the world," said the study's lead author, Robert J. Mayer, MD, faculty vice president for academic affairs, medical oncologist and colorectal cancer researcher at Dana-Farber. "To have a well-tolerated, effective new drug in a cancer that is so prevalent is good news for patients."

The trial, a phase 3 study involving major cancer research institutions in Europe, the United States, Australia and Japan, enrolled 800 patients with metastatic colorectal cancer that was progressing despite previous treatment. Participants were randomly assigned to receive TAS-102 or a placebo pill...

More : http://www.nejm.org/doi/full/10.1056/NEJMoa1414325

Drug combination lengthens lives of metastatic colorectal cancer patients

Keryx Biopharmaceuticals Announces Top-Line Data from the Perifosine (KRX-0401) X-PECT Phase 3 Clinical Trial

Keryx Biopharmaceuticals, Inc. reported today that the Phase 3 "X-PECT" (Xeloda® + Perifosine Evaluation in Colorectal cancer Treatment) clinical trial evaluating perifosine (KRX-0401) + capecitabine (Xeloda) in patients with refractory advanced colorectal cancer did not meet the primary endpoint of improving overall survival versus capecitabine + placebo.

This Phase 3 trial was conducted pursuant to a Special Protocol Assessment (SPA) agreement with the FDA.  468 patients at sixty-five U.S. sites participated in this study. 

Ron Bentsur, Chief Executive Officer of Keryx, stated, "We are all extremely disappointed with the results of the study.  We thank the investigators who participated in what we believe was a well-run study, despite the outcome.  We will evaluate whether our Phase 3 study of Perifosine in relapsed/refractory multiple myeloma will continue as planned."

Mr. Bentsur commented further, "With approximately $31 million in cash as of March 31, 2012, and a well-controlled burn rate, we plan to focus our resources on the pending completion of the Zerenex (ferric citrate) long-term Phase 3 study for end stage renal disease (ESRD) patients with hyperphosphatemia, expected in the fourth quarter of 2012, and the New Drug Application (NDA) filing for Zerenex which will hopefully follow shortly thereafter."

KRX-0401 (perifosine) is in-licensed by Keryx from AeternaZentaris Inc. in the United States, Canada and Mexico.

Ref : http://investors.keryx.com/phoenix.zhtml?c=122201&p=irol-newsArticle&ID=1678920&highlight=

FDAs approval of Lapatinib in combination with Letrozole to treat breast cancer...

In my earlier blog, I mentioned about the combination of Lapatinib and Trastuzumab for breast cancer treatment. Now FDA has  approved Lapatinib in combination with Letrozole (see structure ; Letrozole trade name Femara, an oral non-steroidal aromatase inhibitor for the treatment of hormonally-responsive breast cancer after surgery)  to treat hormone positive and HER2-positive advanced breast cancer in postmenopausal women for whom hormonal therapy is indicated. This drug combination of  Lapatinib  & Letrozole provides women being treated for advanced breast cancer with an important treatment option. 

The entirely oral treatment regimen works by targeting both HER2 and the hormone receptors, thereby slowing the cancer cells' ability to grow or spread. As per the claim by  Dr. Richard Pazdur, (Director, Office of Oncology Drug Products, FDA's Center for Drug Evaluation and Research) women with HER2-positive disease receiving the Lapatinib plus Letrozole combination more than doubled the time they lived without the cancer progressing compared with those receiving Letrozole alone (35 weeks vs. 13 weeks).

Lapatinib, was initially approved in combination with a chemotherapy drug, Xeloda (capecitabine) in 2007. This combination was used to treat women with advanced breast cancer tumors with the HER2 protein who had received prior treatment with chemotherapy drugs, including an anthracycline and a taxane, and Herceptin (trastuzumab), an anti-cancer antibody used to treat HER2-positive advanced breast cancer. Safety information from this study was consistent with previous Lapatinib clinical studies in advanced breast cancer. The most commonly reported side effects of the combination were diarrhea, rash, nausea and fatigue. Still clinical trials are to be carried out, in my opinion its a good achievement...

Ref : http://www.prnewswire.com/news-releases/fda-expands-use-of-approved-breast-cancer-drug-83072502.html

T-DM1 Extends Overall Survival | News | Drug Discovery and Development Magazine

We know that,Trastuzumab emtansine (INN, also called trastuzumab-DM1 or trastuzumab-MCC-DM1, abbreviated T-DM1) is an antibody-drug conjugate consisting of the antibody trastuzumab (the active ingredient in Herceptin) linked to a cytotoxic agent that is a derivative of maytansine (DM1).

It is in clinical trials for breast cancer, especially of the HER2 positive type. Early results in Nov 2011 from an open-label phase II trial on 137 patients with HER2-positive advanced breast cancer were very encouraging.

EMILIA, a phase III trial of 991 people with HER2-positive unresectable locally advanced or metastatic breast cancer, comparing T-DM1 versus capecitabine plus lapatanib in patients previously treated with trastuzumab and a taxane chemotherapy, showed improved progression free survival in patients treated with T-DM1 (median 9.6 vs. 6.4 months) with an improved safety profile. The study sponsor reported in August 2012 that T-DM1 significantly improved survival in the EMILIA study and that the details will be reported at an upcoming medical meeting

T-DM1 Extends Overall Survival | News | Drug Discovery and Development Magazine

Combination of Lapatinib and Trastuzumab a better treatment for breast cancer....

Lapatinib or lapatinib ditosylate is an orally active chemotherapeutic drug treatment for solid tumours such as breast cancer. Patients who meet specific indication criteria may be prescribed lapatinib as part of combination therapy for breast cancer. On March 13, 2007, FDA approved lapatinib in combination therapy for breast cancer patients already using capecitabine.

Recently, researchers from Duke University Medical Center. Dr. Kimberly Blackwell have found more interesting results when they did try the combination of Trastuzumab (monoclonal antibody). As per the claim by the researchers, Lapatinib plus trastuzumab are significantly better than lapatinib alone in extending the lives of breast cancer patients whose tumors are HER2-positive.

Blackwell says, the combination targeted therapy gave patients more than a four-month survival advantage over those who took lapatinib alone. She says the findings may be the first step toward a chemotherapy-free future. This is the first time that a pair of targeted therapies has been shown to be superior to any intervention that paired a targeted therapy with a hormonal or chemotherapy based approach, she said. The interesting claim by the researchers trastuzumab binds to and blocks part of the HER2 growth factor that appears on the surface of some breast cancer cells while lapatinib binds to a second growth factor, EGFR, and part of HER2 that sits below the cell surface. It's sort of a double whammy, disabling the HER2 protein in two places instead of one......

Ref : http://www.dukehealth.org/health_library/news/targeted_therapy_prolongs_life_in_patients_with_her2_positive_breast_cancer

Eribulin drug has minor added benefit in one patient group, indication of lesser benefit in others

In continuation of my update on Eribulin

Eribulin (trade name: Halaven) is approved for women with locally advanced or metastatic breast cancer in whom the disease has progressed despite prior drug therapy. The German Institute for Quality and Efficiency in Health Care (IQWiG) examined in a dossier assessment whether the drug offers an added benefit over the appropriate comparator therapy in these patient groups.

According to the findings, there are both positive and negative effects. There is proof of minor added benefit for one group of patients. For other groups, there are hints or indications of lesser benefit.

Second assessment of eribulin

IQWiG already presented a dossier assessment of eribulin in February 2012. The subsequent decision on the added benefit made by the Federal Joint Committee (G-BA) was limited until April 2014. In addition, the drug manufacturer meanwhile obtained approval for an expanded therapeutic indication: In March 2011 eribulin was only available for patients who have progressed further after at least two chemotherapeutic regimens. Since June 2014, however, the drug can already be used after one unsuccessful treatment attempt. Hence there were two reasons ─ independent from each other ─ for the reassessment of eribulin.

G-BA specified appropriate comparator therapies

When the G-BA specified the appropriate comparator therapy, it distinguished between several treatment situations: The first one refers to patients who are not eligible for further chemotherapy with a taxane or an anthracycline. In this situation, eribulin was to be compared with individual chemotherapy containing the drugs capecitabine or vinorelbine.

In patients for whom taxanes or anthracyclines are principally still an option, eribulin was to be compared with an individual chemotherapy containing a taxane or an anthracycline.

Eribulin drug has minor added benefit in one patient group, indication of lesser benefit in others

Eribulin mesylate drug may help extend lives of women with advanced breast cancer..

We know that, Eribulin (see structure E7389) is an investigational  anticancer drug. Eribulin was previously known as E7389.  Eribulin is currently being investigated by Eisai Co. for the third-line treatment of advanced breast cancer in patients who have been previously treated with anthracyclines, taxanes and capecitabine, as well as a variety of other solid tumors, including non-small cell lung cancer, prostate cancer and sarcoma.

Structurally, eribulin is a fully synthetic macrocyclic ketone analogue of the marine sponge natural product halichondrin B a potent mitotic inhibitor with a unique mechanism of action found in the Halichondria genus of sponges. Eribulin is a mechanistically-unique inhibitor of microtubule dynamics, exerting its anticancer effects by triggering apoptosis of cancer cells following prolonged mitotic blockage. A new synthetic route to E7389 was published in 2009.

Now   research team at the University of Leeds and St James's Institute of Oncology led an international trial of the new chemotherapy drug, eribulin mesylate. As per the claim by the researchers, average survival was typically 25 per cent longer for women who took eribulin mesylate.

In the EMBRACE trial, 762 patients with advanced breast cancer received either eribulin or standard cancer treatment. All of the patients had already been heavily treated with conventional therapies, but their disease had returned or spread to other parts of the body.  Researchers concluded that those who took the new drug lived for 13.1 months, on average, compared with 10.7 months for those on conventional chemotherapy. The drug was also well-tolerated by most patients. Researchers hope that these results may establish eribulin as a new, effective treatment for women with late-stage metastatic breast cancer (either single drug or in combination with other anticancer drug). The drug is not yet available for routine clinical treatment and is awaiting regulatory approval in the European Union, the US and Japan.

"Until now, there hasn't really been a standard treatment for women with such advanced breast cancer. For those women who have already received all of the recognised treatments, these are promising results, claims the lead investigator Professor Christopher Twelves...

Ref : http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=50309

FDA Approves Kadcyla for Late-Stage Breast Cancer

We know that, Trastuzumab emtansine  in the United States, ado-trastuzumab emtansine, trade name Kadcyla) is anantibody-drug conjugate consisting of the monoclonal antibody trastuzumab (Herceptin) linked to the cytotoxic agentmertansine (DM1). Trastuzumab alone stops growth of cancer cells by binding to the HER2/neu receptor, whereas mertansine enters cells and destroys them by binding to tubulin. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the toxin specifically to tumor cells.

In the EMILIA clinical trial of women with advanced HER2 positive breast cancer who were already resistant to trastuzumab alone, it improved survival by 5.8 months compared to the combination of lapatinib and capecitabine. Based on that trial, the U.S. Food and Drug Administration (FDA) approved marketing on February 22, 2013.

Trastuzumab emtansine was developed by Genentech. The planned cost is expected to be $9,800 a month, or $94,000 for a typical course of treatment..

Now....

FDA Approves Kadcyla for Late-Stage Breast Cancer