AstraZeneca announced that a new phase-III study of novel once-daily oral anticancer drug vandetanib (Zactima), is underway to investigate the addition of vandetanib to pemetrexed (Alimta) as second-line treatment for patients with locally advanced or metastatic nonsmall-cell lung cancer (NSCLC) after failure of first-line anticancer treatment. Dubbed as Study 36, it will be conducted across 20 countries worldwide.

    As its primary objective, Study 36 will evaluate progression-free survival with vandetanib 100 mg plus pemetrexed 500 mg/m2 compared with pemetrexed 500 mg/m2 plus placebo in patients with advanced NSCLC, who have previously received anticancer treatment. The study will also assess overall survival, objective response rate, disease-control rate, duration of response, effect on disease-related symptoms, time to deterioration of disease-related symptoms, the safety and tolerability of vandetanib in combination with pemetrexed, and population pharmacokinetics of vandetanib

    "After treatment failure with initial therapy, response rates to further treatment is low in patients with advanced nonsmall-cell lung cancer," commented Dr. Richard de Boer of Australia's Western Hospital, principal investigator. "The effect of combining novel targeted agents such as vandetanib with chemotherapy needs to be explored to progress treatment options for patient benefit."

    Vandetanib works by inhibiting both the development of the tumor's blood supply through inhibition of vascular-endothelial-growth-factor receptor (VEGFR) and the growth and survival of the tumor itself through inhibition of EGFR. It also inhibits RET kinase, an important growth factor in certain types of thyroid cancer. Vandetanib has shown promising antitumor activity in NSCLC when used alone and in combination with docetaxel in phase-II trials. It has been awarded orphan drug status in the United States and European Union. M AZ Press Office

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Glivec lowers GIST recurrence

 

 

BASEL, Switzerland

Investigators will begin offering imatinib (Glivec) to patients receiving placebo in a major North American clinical trial after an interim analysis showed participants with Kit-positive gastrointestinal stromal tumors (GIST) treated with Glivec following surgery were significantly less likely to experience a return of their cancer.

    The interim analysis showed no recurrence of cancer in 97 percent of patients given Glivec for a year after surgery to remove tumors, compared with 83 percent of those who underwent surgery but received a placebo. The investigators made the results public in March because the study had met its primary end point in terms of the rate of recurrence-free survival.

    The study involving more than 600 patients was sponsored by the National Cancer Institute (NCI), which is part of the United States National Institutes of Health (NIH). It was conducted at multiple cancer centers in the US and Canada, and was led by the American College of Surgeons oncology group. Novartis supplied Glivec for use in the study, and also provided partial funding under a cooperative research and development agreement with NCI.

    Glivec has already been confirmed as an effective therapy in its approved use for patients with advanced metastatic or unresectable Kit-positive GIST.

    "With these new data, we see that Glivec may help patients with early GIST," commented Dr. Diane Young, head of global medical affairs at Novartis Oncology. "We will now work with the investigators on a submission to gain regulatory approval for Glivec as adjuvant treatment for GIST."

    Following the recommendation of a data-monitoring committee, the study will be closed and patients in the study who are currently being treated with placebo may choose to receive one year of Glivec.

    In the study, patients were randomized to one of two treatment arms. Neither the patients nor physicians knew which treatment the patients were receiving. One patient group received Glivec at a dose of 400 mg per day for one year, while the second group received placebo for one year. Patients who developed a recurrence of their cancer while on a study therapy were unblinded to their treatment assignment. Those receiving placebo subsequently received Glivec, while those already given Glivec continued at a higher dose.

    Glivec is approved in more than 90 countries for the treatment of all phases of Ph+ chronic myeloid leukemia (CML). Glivec is also approved in the European Union, US, and other countries for the treatment of patients with Kit-positive GIST, which cannot be surgically removed or have already metastasized. In the EU, Glivec is also approved for the treatment of adult patients with newly diagnosed Ph+ acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy and as a single agent for patients with relapsed or refractory Ph+ ALL. M

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New applications for Januvia sought

 

 

WHITEHOUSE STATION, New Jersey

Merck & Co. Inc. said that the United States Food and Drug Administration (FDA) has accepted for standard review two supplemental new drug applications for sitagliptin (Januvia), and the company expects action on both by mid-October.

    One application is for a proposed new indication for Januvia as an adjunct to diet and exercise, in combination with metformin as initial therapy to improve glycemic control. The other is for two proposed new indications for Januvia as an adjunct to diet and exercise, as add-on therapy to a sulfonylurea when the single agent alone does not provide adequate glycemic control, and as add-on therapy to the combination of a sulfonylurea plus metformin when dual therapy does not provide adequate glycemic control.

    Januvia is currently indicated for use as monotherapy and as add-on therapy to either of two other types of oral diabetes medications-metformin or thiazolidinediones-to improve blood-sugar control in patients with type 2 diabetes. The recommended dose is 100 mg once daily.

    "If these [applications] are approved, the expanded labeling will include indications for use of Januvia as initial therapy with metformin and as add-on to any of the three most commonly prescribed classes of oral antihyperglycemic agents," said Dr. John Amatruda, vice president for clinical research at Merck. "These data further support the broad utility of Januvia as an important treatment option for patients with type 2 diabetes."

    The proposed new indication for Januvia in combination with metformin is supported by a 24-week factorial study in 1,091 randomized patients with type 2 diabetes. The study showed a significant mean placebo-subtracted reduction in A1C1 of 2.1 percent from a mean baseline A1C of 8.7 percent (primary analysis of all patients treated, p > 0.001) in the patients treated with Januvia 50 mg twice daily combined with metformin 1,000 mg twice daily (n = 178). In the same study, 66 percent of patients treated with Januvia 50 mg twice daily combined with metformin 1,000 mg twice daily achieved goal A1C levels of <7 percent compared with 38 percent of patients treated with metformin 1,000 mg twice daily alone (p < 0.01).

    The proposed new indications for Januvia as an add-on to a sulfonylurea or to sulfonylurea and metformin are supported by a 24-week study involving 441 patients with type 2 diabetes who had inadequate glycemic control on a sulfonylurea alone or a sulfonylurea plus metformin. M

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Roche introduces Neulastyl locally

 

 

Roche Philippines recently introduced the long-acting formulation of a support treatment that has been in use for 16 years as prophylaxis for neutropenia, a major dose-limiting side effect of cytotoxic cancer chemotherapy. Neutropenia is a condition marked by a dangerously low white-blood-cell count and is induced by the suppression of blood-cell production by cytotoxic drugs, possibly leading to various complications and even death. By limiting chemotherapy dose, it can also pull down therapeutic outcome to below optimum level.

    Pegfilgrastim (Neulastyl) is the pegylated or sustained duration form of filgrastim, a recombinant, nonglycosylated granulocyte-colony-stimulating factor (G-CSF) that has been licensed for use since 1991. G-CSF is a protein normally produced by the body to stimulate the bone marrow to produce neutrophils, the most common type of white blood cells.

    With a half-life of 33 hours compared with filgrastim's 3.5 hours, pegfilgrastim needs only to be administered once per chemotherapy cycle. The recommended dose is a single, fixed six milligrams per cycle, which is effective across a broad range of body weights, according to oncology expert Dr. Ruth Pettengell of London's St. George's Hospital Medical School. Pettengell was the guest lecturer during the product launch.

    "Neulastyl is indicated to decrease incidence of infection, as manifested by febrile neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive anticancer drugs associated with a significant incidence of severe neutropenia with fever," she said.

    Dr. Susano Tanael of the University of the Philippines-Philippine General Hospital explained that the technology of pegylation enables the new drug formulation to stay in the body for a longer period of time by reducing renal clearance while the neutrophil level is dipping. "It will take an equivalent of five to six days for the pegylated version to go through all its half lives. So if you give it 24 hours after the start of the chemo treatment, it would be preventing the lowest dip in neutrophil levels which usually occurs in seven to 10 days."

    According to Pettengell, G-CSF in general is recommended by the US National Comprehensive Cancer Network for patients with more than 20-percent overall risk for neutropenia. The American Society of Clinical Oncology advocates a risk threshold of 40 percent for routine G-CSF support in patients with solid tumors and nonmyeloid malignancies.

    Although no cost-benefit study has yet been developed in the local setting, international expert opinion cites lower cost of administration for pegfilgrastim through reduced professional fees and hospital visits. Tanael also cited the lower hospitalization cost that can be attributed to lesser management of adverse events.

    Dr. Rolf Ammelburg, Roche Philippines general manager, noted that Neulastyl is one more quality step in a never-ending journey of innovation for the company, particularly in the field of oncology. "Neulastyl is an exciting addition to our targeted oncology therapeutics, a novel addition to our extensive amount of supportive treatments," he said. M Grace Roxas

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Biocon bares cheap kidney drugs

 

 

BANGALORE, India

India's largest biotechnology firm, Biocon Ltd., launched a range of cheap drugs to treat kidney diseases. Bangalore-based Biocon, which unveiled the drugs on World Kidney Day, said it plans to market five medicines in several countries at least 30-percent cheaper than those sold by larger drug companies.

    "We are committed to developing affordable drugs of high quality," said Kiran Mazumdar-Shaw, who heads Biocon and is reputed to be India's richest woman. "Kidney disease is life-threatening and is on the increase, while treatment is expensive."

    In India, a nation of 1.1 billion people, up to 100,000 are affected with kidney diseases such as renal failure every year, according to Biocon, which billed it as the "silent epidemic of the 21st century."

    The international market for kidney drugs is estimated at an annual US$3.3 billion and India, where only 20 percent of the patients can afford treatment, accounts for about US$70 million.

    Biocon also plans to target the Persian Gulf region and Latin America, said Mazumdar-Shaw, adding it may offer some of the products for overseas companies to manufacture under license.

    The drugs were launched by Sudha Murthy, wife of N.R. Narayana Murthy, chief mentor of Indian software maker Infosys Technologies and the elder statesman of the industry. M AFP

 

 

 

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