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COMMENTARY |
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U.S. National Cancer Institute Plans Fresh Look at Mammography for Younger Women |
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 Top U.S. National Cancer Institute... Swedish Studies: 23% Reduction...Advisors to US FDA...New Products |
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The Institute has begun planning a consensus conference to be held later this year to evaluate new data from clinical trials, Klausner said to The Cancer Letter.
NCI would invite a panel of experts to Bethesda, MD, to evaluate data from Swedish studies as well as a meta-analysis published by US investigators earlier this year, Klausner said. Those data have become available since NCI’s 1993 decision to withdraw its support for screening women in their forties.
"The consensus conference would look at all of the data that is now available, specifically in light of the meta-analysis, and the new data from the five Swedish studies," Klausner said in an interview.
Swedish investigators presented new data from five breast cancer screening trials at a scientific meeting held last month in Falun, Sweden. The data appear to show that women in their forties screened for breast cancer had a statistically significant reduction in their risk of dying from the disease, participants of the meeting said.
The purpose of the NCI consensus conference would not be to critique the Institute’s 1993 statement, made under the former NCI director, Klausner said. "I’m not interested in re-evaluating previous decisions by previous NCI directors," Klausner said to The Cancer Letter. "What I’m interested in is constantly evaluating the data, and acting on new data as new data becomes available."
Klausner said he has spoken to the Swedish investigators and encouraged them to publish their results as soon as possible. "From the reports, the Swedish data looked very impressive," Klausner said. "However, it is important that we analyze the data, and not just reports of the data." 
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Swedish Studies: 23% Reduction in Deaths |
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TopU.S. National Cancer Institute...Swedish Studies: 23% Reduction...Advisors to US FDA...New Products |
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Overall, women who received a mammogram had a 23% reduction in deaths from breast cancer, compared to those who did not receive a mammogram. The data were statistically significant.
In one trial, based in Gothenburg, Sweden, women in the screened group had a 41% reduction in deaths from breast cancer, compared to the unscreened group.
Edward Sondik, Deputy Director of the NCI Division of Cancer Prevention and Control, attended the Falun conference. "The Swedish investigators’ presentation showed that point estimates of screening effectiveness have shifted from their earlier figures toward indicating a higher level of effectiveness and that the confidence intervals had narrowed," Sondik said to The Cancer Letter.
"Especially intriguing were the results from Gothenburg indicating a 40% reduction in breast cancer deaths at just about statistical significance," Sondik said. "However, no details on Gothenburg were presented, other than the overall result. Gothenburg had relatively few breast cancer deaths, but the results are still important.
"I hope the investigators publish these results quickly and that the community can meet and consider them in light of follow-up from other trials," he said.
Earlier this year, a group of US investigators published a meta-analysis of seven trials worldwide demonstrating that women in their forties who received screening mammography had a 24% reduction in death from breast cancer (Smart et al., Cancer 1995;75:1619-1626).
The controversy over whether women in their forties should get regular mammograms to screen for breast cancer divided the US oncology and patient advocacy community when NCI withdrew its support for screening guidelines developed in 1988 with the American Cancer Society and other US health organizations.
In December 1993, NCI issued a "Summary of Scientific Fact," which made no recommendation about screening mammography for women in their forties, but affirmed women 50 and over should get annual mammograms.
Less than one month earlier, ACS and 18 other professional and patient advocacy groups reaffirmed their support for the 1988 guidelines, which call for annual screening mammography and clinical breast examination for women over 50, and the same procedures every one to two years for women between the ages of 40-49.
The Secretary of the US Department of Health and Human Services, Donna Shalala, acknowledged that NCI might have handled the controversy more smoothly. "We tripped over ourselves and probably confused a whole generation of women," she said shortly after NCI issued its statement.
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Advisors to US FDA Recommend Approval of Topotecan for Ovarian Cancer |
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TopU.S. National Cancer Institute...Swedish Studies: 23% Reduction...Advisors to US FDA...New Products |
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The FDA Oncologic Drugs Advisory Committee (ODAC) voted 8-0 to recommend marketing approval for Hycamtin, based on a review of data from two large international, multicenter trials conducted on patients with recurrent ovarian cancer.
Hycamtin is the first topoisomerase I inhibitor to be recommended for approval in the US. The drug inhibits the enzyme topoisomerase I, which is involved in the replication of DNA in human cells.
ODAC members said they agreed with the company’s assertion that the data from the studies demonstrated that the new drug is at least as effective as paclitaxel (Taxol, Bristol-Myers Squibb Co.), the current standard therapy.
The company presented data from a phase III trial involving 226 women with recurrent ovarian cancer after first-line platinum therapy.
Patients were randomized to a 30-minute infusion of Hycamtin 1.5 mg/m2/day for five days or to a three-hour infusion of paclitaxel 175 mg/m2 every 21 days. The Hycamtin group consisted of 112 patients. The paclitaxel group had 114 patients.
In the Hycamtin arm, 4.5% of patients had a complete response and 16% had a partial response. In the paclitaxel arm, 2.6% had a complete response and 10.6% had a partial response.
The median response duration was 32 weeks for Hycamtin and 19.7 weeks for paclitaxel. The median time to progression was both statistically and clinically significant, indicating that patients receiving Hycamtin experienced progressive disease less rapidly—23 weeks compared to 14 weeks for paclitaxel.
The median survival was 61.3 weeks for Hycamtin and 42.6 weeks for paclitaxel. The difference in survival was not statistically significant.
The trial included a cross-over design that allowed patients on either arm to choose the other arm following initial therapy. Three patients who failed to respond on the paclitaxel arm responded to Hycamtin, said Maurie Markman, director of the Cleveland Clinic Cancer Center.
In a phase II noncomparative multi-center study in 111 women with recurrent ovarian cancer after first-line platinum therapy, the objective response rate was 14.4%. The median duration of response was 16.3 weeks. The median time to progression was 11.3 weeks and the median survival was 52.4 weeks.
In the study, the median time to response was 10.4 weeks. FDA reviewer Steven Hirschfeld said oncologists using Hycamtin should give adequate time to treatment before ceasing therapy due to lack of response.
The efficacy of Hycamtin was confirmed in the two additional open noncomparative studies included in the file submitted to the committee, the company said. The two studies were not presented at the meeting.
In each study, the dosage of Hycamtin was 1.5 mg/m2 administered intravenously over 30 minutes daily for five days and repeated every 21 days.
Suppression of blood cells produced in the bone marrow, the principal side effect demonstrated by Hycamtin in clinical trials, was predictable, noncumulative, reversible and manageable, the company said in its presentation.
Combining the data from all four ovarian cancer studies, 18 of 445 patients (4%) withdrew from study due to hematologic or infective complications.
Grade 4 neutropenia occurred in 79.5% of patients in all four trials. Grade 4 thrombocytopenia occurred in 23.4%. Grade 3 and 4 anemia occurred in 36.8% of patients. Fever or infection with grade 4 neutropenia occurred in 20.7%. Sepsis occurred in 4.7% of patients. Three patients died due to neutropenia. The most frequently reported nonhematologic side effects were gastrointestinal, including nausea and vomiting.
In the phase III trial, no statistically significant difference was observed between Hycamtin and paclitaxel in quality of life as measured by 15 parameters.
ODAC voted unanimously that the toxicity profile of Hycamtin was acceptable for patients with recurrent ovarian cancer. SmithKline Beecham has begun a first-line combination chemotherapy study with Hycamtin in patients with ovarian cancer. Hycamtin is also being studied for a number of other tumor types, the company said.
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New Products |
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TopU.S. National Cancer Institute...Swedish Studies: 23% Reduction...Advisors to US FDA...New Products |
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Fareston is a once-daily oral anti-estrogen that binds to estrogen receptors in cancer cells, thereby blocking estrogen from further stimulating tumor growth.
The EU marketing authorization is immediately valid in the 15 EU member states.
Immunex Corp.
of Seattle, WA, said it plans to begin to market Truquant BR RIA to oncologists in the US, as part of a co-marketing agreement with Biomira Diagnostics, Inc. of Toronto, Canada.
Earlier this month, FDA granted marketing clearance of Truquant BR RIA to Biomira, the manufacturer of the blood test. Truquant BR RIA is the first breast tumor marker test to receive expedited review by the FDA, and is the first such test to be cleared for marketing in the US, the company said.
Truquant BR RIA detects breast cancer recurrence in women previously treated for stage II and stage III breast cancer, the company said. The test works by detecting CA27.29 antigen in the blood. CA27.29 antigen is present on breast cancer cells and is shed into the bloodstream in high levels as breast cancer metastasizes.
Routine monitoring for CA27.29 antigen with Truquant BR RIA should be used in conjunction with other clinical methods for the early detection of breast cancer recurrence, the company said.
The test was recently evaluated in a three-year prospective, double-blind, multicenter clinical trial of 166 breast cancer patients with stage II or stage III breast cancer who were clinically free of the disease at the time of enrollment.
The company said positive results with Truquant BR RIA could predict with high probability the recurrence of the disease. The study demonstrated that if the Truquant BR test was positive, a recurrence occurred 99% of the time.
ATL of Bothell, WA, said it has received FDA premarket approval (PMA) for ultrasound imaging of breast tumors.
The breast ultrasound procedure, when used as an adjunct to mammography and physical examination, helps to determine whether a biopsy is needed for suspicious breast lesions, the company said.
According to the company, the new ultrasound application may reduce the number of breast biopsies performed by over 40%.
FDA acted upon the recommendation of its Radiology Advisory Panel.
The company’s PMA application was based on the findings of an international multi-center study involving over 1,000 women with breast lesions. According to the company, clinical investigators found that the number of breast biopsies could be reduced by approximately 40% by using the ATL High Definition Imaging digital ultrasound to distinguish benign from malignant lesions that were found indeterminate by mammography and physical examination.
The 15-minute examination will be performed following diagnostic mammograms of suspicious breast lesions.
Immunomedics, Inc.
of Morris Plains, NJ, said it has received an approvable letter from FDA for CEA-Scan, the company’s diagnostic imaging product for colorectal cancer. Final marketing approval of CEA-Scan is subject to FDA approval of product labeling.
CEA-Scan comprises an antibody fragment against the tumor marker, carcinoembryonic antigen. CEA is expressed by more than 90% of colorectal cancers, as well as by a large number of other carcinomas, including esophageal, stomach, lung, breast, pancreas, uterus, and ovarian cancer, and it has been shown that this tumor marker can serve as a useful target for radiolabeled antibodies.
Since CEA-Scan uses a small antibody fragment at a low dose, there is virtually no immune reaction by patients to the foreign protein, the company said.
In addition, linking the fragment with technetium-99m, a common radioisotope in nuclear medicine, permits tumor detection within a few hours, using conventional gamma cameras.
Hoechst Marion Roussel of Kansas City, MO, said it has submitted New Drug Applications with FDA for Anzemet (dolasetron mesylate), proposed for the prevention of nausea and vomiting in patients undergoing single or repeated courses of emetogenic cancer chemotherapy.
Available in once-a-day oral or i.v. dosing, Anzemet is also proposed for the prevention and treatment of nausea and vomiting in patients undergoing surgery, the company said.
Anzemet is a 5-HT3 receptor antagonist, a drug that targets the sensory centers in the body that, when stimulated, trigger nausea and vomiting. By intercepting the connection of the neurotransmitter serotonin to receptors in the gastrointestinal tract and the brain, these drugs break the nerve impulse that triggers vomiting.
IDEC Pharmaceuticals Corp.
of San Diego said that Chugai Pharmaceutical Co., Ltd. of Japan has licensed IDEC’s proprietary vector technology for high expression of recombinant proteins in mammalian cells.
Under the agreement, Chugai will pay an upfront licensing fee of $4.5 million to IDEC, as well as royalties on sales of Chugai products manufactured using the technology.
The agreement with Chugai is the second platform license that IDEC has executed for this high-yield gene expression technology. The first licensee was Genentech Inc., IDEC’s partner on the development of IDEC-C2B8 and IDEC-Y2B8, immunotherapies for non-Hodgkin’s B cell lymphomas.
Two additional platform licenses remain available. IDEC also undertakes individual cell line development projects using this technology and has executed product-specific contract agreements with Biogen, F. Hoffmann-La Roche, Ltd. and Pharmacia & Upjohn, Inc.
NeXstar Pharmaceuticals, Inc.
of Boulder, CO, said FDA has approved the company’s new drug applications for the anticancer drug DaunoXome (daunorubicin citrate liposome injection), as a first-line cytotoxic therapy for the treatment of advanced, HIV-associated Kaposi’s Sarcoma.
NeXstar plans to launch DaunoXome shortly at a price competitive with conventional therapy. DaunoXome is formulated to maximize the selectivity of daunorubicin for solid tumors in the body.
In granting approval for DaunoXome, the FDA noted that the drug was as effective as the current three-drug regimen of adriamycin, bleomycin and vincristine (ABV) but that DaunoXome therapy reduced the incidence of side effects that can adversely affect a patient’s quality of life. In addition, review of NeXstar’s phase III data led the FDA to conclude that DaunoXome therapy reduces the cardiotoxicity normally associated with anthracycline-based chemotherapy.
NeXstar presented data from its phase III clinical trial at the FDA’s Oncologic Drugs Advisory Committee. The phase III trial was a controlled, randomized study of 227 HIV-positive patients with advanced Kaposi’s Sarcoma. The study compared the efficacy and side effects profile of DaunoXome and a three-drug regimen of adriamycin, bleomycin and vincristine. Based on its review, the advisory committee recommended that DaunoXome be approved as a first-line therapy.
Sequus Pharmaceuticals, Inc.
of Menlo Park, CA, said its drug Amphocil has been approved in Holland, bringing to nine the number of countries in which Amphocil has been authorized for sale. Marketing clearance for Amphocil has previously been granted in Brazil, the Czech Republic, Denmark, Ireland, Finland, Russia, Singapore and the UK.
An NDA was filed in the US in late 1995; additional marketing approvals are pending in several member states of the European Union.
Amphocil has been approved for the treatment of systemic fungal infections in patients for whom conventional therapy is contraindicated due to toxicity or renal failure or for whom previous antifungal therapy was unsuccessful.
In addition to its use as a second-line therapy for systemic fungal infections, Sequus is developing Amphocil for use in treating infections that often afflict immunocompromised patients.
The company is conducting clinical trials of Amphocil in the US, including the only double-blind, randomized trial comparing a lipid-based amphotericin B compound with conventional amphotericin B in patients with documented aspergillosis, a doubleblind study comparing Amphocil with amphotericin B in patients with febrile neutropenia who have not responded to antibiotic treatment, and a compassionate-use protocol for patients with systemic fungal infections who are intolerant or unresponsive to other therapeutic agents.
Amphocil will be marketed and sold in Holland by Zeneca Pharmaceuticals under a distribution agreement with Sequus.
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