Hatch Kennedy Bill To Help Millions Suffering From Traumatic Brain Injury

Sen. Edward Kennedy's battle with a malignant brain tumour (glioblastoma multiforme) is likely to put a dramatic personal stamp on a health care cause he first championed nearly 40 years ago: The nation's war on cancer.

Kennedy had already begun work on an overhaul of the 1971 National Cancer Act when his tumour was diagnosed, and advocates hope the fact that Kennedy has fallen victim to this disease will generate public support and lend new urgency to the need to update the bill. The 76-year-old Kennedy has been a prominent and passionate advocate of cancer research and other health care issues throughout his long tenure in the Senate.

His name has become virtually synonymous with the push for universal health care coverage. He was a leader in enacting several landmark bills, including the Americans with Disabilities Act of 1990, the State Children's Health Insurance Program and the Kennedy-Kassebaum bill protecting workers from losing health insurance when they switch jobs, or from being denied coverage due to pre-existing conditions. He's been instrumental in promoting biomedical research, AIDS research and treatment, a national bone marrow donor registry and anti-tobacco bills.

Kennedy has been working closely with Republican Sen. Kay Bailey Hutchison of Texas and plans to file the legislation in the coming weeks. As one of the Senate's shrewdest legislators and dealmakers, Kennedy is known for joining forces with Republicans to win passage of major bills.

The bill Kennedy plans to put forth seeks to improve the coordination of cancer research, prevention and treatment while giving more money to the National Cancer Institute and other public research agencies.

Congress is on a Memorial Day recess, and it is unclear when Kennedy, chairman of the Senate Health, Education, Labor and Pensions Committee, will be back on Capitol Hill. He returned to his family's Hyannis Port, Mass. compound last week after being released from Massachusetts General Hospital in Boston.

Kennedy emerged as a leader in winning passage of the National Cancer Act after he became chairman of the Senate's health subcommittee in 1971. At the time, there was wide concern about cancer as the nation's second leading cause of death.

His family has been touched by cancer over the years; two of his children, Kara and Edward Kennedy Jr., are cancer survivors. Edward Kennedy Jr. lost a leg to bone cancer in 1973 at age 12, and Kara was diagnosed with lung cancer five years ago. Both were given a 15 percent chance of survival, but are cancer-free now. The senator threw himself into their care, finding the best medical advice and treatment options for them.

A few weeks ago, Kennedy and Hutchison teamed up with seven-time Tour de France winner and cancer survivor Lance Armstrong at a Senate hearing and a news conference calling on Congress and the country to step up the fight against cancer. The events were aimed at building support for the bill. Kennedy mentioned how his children overcame the disease. When Kennedy's diagnosis was revealed, Armstrong said renewing the fight against cancer would be a good way to honour the senator.

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Hatch-Kennedy Bill

Cancer drug sales may rise to $80 billion by 2011

The global market for cancer drugs will grow twice as fast as that for all other pharmaceuticals as the developing world spends more on health care. It could reach $80 billion by 2012, according to IMS Health, which tracks prescription drug sales.

IMS noted that expensive new treatments, coupled with an increasing number of patients on chemotherapy in major markets and evidence that more people in emerging markets are gaining access to modern targeted therapies will contribute to sales of cancer drugs growing at a compound rate of 12 to 15 percent.

In 2008, sales of oncology products will exceed $48 billion, contributing nearly 17 percent of global pharmaceutical sales growth this year, led by Genentech's breast cancer drug Herceptin, Novartis' leukemia drug Gleevec and other blockbusters, according to IMS.

The cancer market may see double-digit sales growth, fueled by increased use of targeted therapeutic agents introduced over the past 10 years, along with first-time innovations coming to the market and chronic treatment for growing numbers of patients. China, Brazil, Russia and other emerging countries are also becoming bigger customers for pharmaceuticals as they invest more in treating and diagnosing cancer.

IMS expects growth to be fueled by the introduction of 25 to 30 new chemical entities between 2008 and 2012, as expensive new biotechnology drugs and the increasing use of combination therapies contribute to the exploding cost of treatment.

Data from clinical studies of many of the newest cancer drugs will be presented and discussed at the nation's largest oncology meeting later this month in Chicago. Much of the data will be unveiled on Thursday ahead of the American Society of Clinical Oncology meeting.

There are several factors that could moderate growth over the next five years. They include financial constraints of payers, slowing growth of some current blockbuster therapies and patent expirations of four cancer drugs with annual sales exceeding $1 billion, including Eli Lilly's Gemzar and Taxotere from Sanofi-Aventis.

Are ESA's safe enough for cancer patients?

Earlier this year the FDA held a fourth session with the Oncologic Drugs Advisory Committee (ODAC) to review erythropoietin stimulating agents (ESA's). In 1993, ESA's were approved to reduce the number of red blood cells transfusions in cancer patients who have chemotherapy induced anemia. There is no doubt that the drugs do reduce the number of transfusions. They are also believed to alleviate symptoms such as fatigue and improve quality of life associated with the anemia, although the FDA has said that these remain 'unproven'.

The biggest challenge facing ODAC and the FDA though, is deciding whether ESA's very benefit in anemia is also a negative in terms of increased mortality and/or tumour progression. Eight controlled clinical trials suggest that there is evidence of increased risk of mortality and tumour progression in patients who have head & neck cancer, breast cancer, non-small cell lung cancer (NSCLC) and cervical cancer. According to the FDA, the new studies are either much larger than the original ones used to establish safety of the ESA's or have a different underlying histology.

In addition, the FDA claims that there is insufficient data to rule out mortality, shorter time to progression or lower loco-regional control in cancer other than NSCLC. As a result, FDA have asked ODAC to consider the following options:

- Remove the indication to treat anemia caused by cancer chemotherapy
- Restrict the indication to only patients who will not be cured by treatment intervention and contraindicate in adjuvant therapy
- Restrict use to specific cancer sub-types where safety has been adequately assessed (only NSCLC)
- Contraindicate use where harmful effected have been demonstrated (breast and head & neck cancers)
- Mandate risk management strategies

What is clear is that ESA's do offer a valuable clinical benefit in chemotherapy-induced anemia when used appropriately to avoid transfusions. The question is really one of risk-benefit because the very mechanism by which they work might also induce negative consequences.

It will be interesting to see what happens; The ESA market is worth several billion a year and sales are likely dropping with the repeated FDA discussions about risk benefit and safety.

Poniard report encouraging data in several cancers

The results of the Phase I trials with picoplatin, a new generation platinum, in prostate and colorectal cancer were presented earlier this year. Encouraging bioavailability data has also been presented from the ongoing Phase I trial of oral picoplatin.

The final phase II efficacy results in SCLC confirmed previously announced interim results showing a survival benefit in patients with recurrent SCLC who failed prior platinum-containing first-line chemotherapy or who progressed within six months of first-line therapy. The median overall survival in the picoplatin Phase II trial was 27 weeks for refractory and resistant small cell lung cancer patients, a population for which there is no approved therapy in the US.

The pivotal Phase III SPEAR trial in small cell lung cancer continues to enroll patients and patient enrollment in the Phase II trial in metastatic colorectal cancer has now completed.

Poniard's Chief Medical Officer stated that:

"Picoplatin, to date, has demonstrated good tolerability, with no severe neuropathies when combined with 5-fluorouracil and leucovorin in the FOLPI regimen. In our Phase 2 trial, we are performing a head-to-head comparison of the efficacy and safety of picoplatin with oxaliplatin. We will be presenting preliminary Phase 2 data and updated Phase 1 data at the 2008 American Society of Clinical Oncology (ASCO) Annual Meeting."

In 2005, the importance of KRAS mutations in the development of resistance to treatment with gefitinib (Iressa) and erlotinib (Tarceva) in non-small cell lung cancer (NSCLC) were first reported by Pao and colleagues.

The same year, another study (Moroni et al., ) assessed the relationship between epidermal growth factor receptor (EGFR) gene copy number, and KRAS and BRAF mutations as biomarkers of response to EGFR-targeted monoclonal antibodies for metastatic colorectal cancer.

The study found that in patients treated with cetuximab (Erbitux) or panitumumab (Vectibix), a correlation existed between clinical response and tumour EGFR copy number, and that KRAS or BRAF mutations occur mainly in patients with metastatic colorectal cancer resistant to treatment with these drugs.

Subsequent studies confirmed the association of KRAS mutations and resistance with such compelling evidence that led to the approval of panitumumab in Europe for the treatment of KRAS wild-type only metastatic colorectal cancer. As for EGFR copy number, later studies also confirmed an association with clinical outcome.

In a recent article, Moroni et al., conceded that the new challenge in metastatic colorectal cancer is that EGFR FISH pattern is often not homogeneous and has variable ratios, which makes the scoring of EGFR signals and defining the EGFR pattern by FISH difficult. Standardisation of methods is, therefore, needed to reach better reproducibility and optimum sensitivity.

As the authors explained, "From a clinical point of view, we can risk treating a non-responsive patient, but we cannot risk not treating a potentially responsive one."

Do vitamin D receptors influence the risk of breast cancer?

Certain vitamin D receptor (VDR) gene polymorphisms could affect the risk of breast cancer, as well as the estrogen receptor status of tumours in postmenopausal women, according to findings from a German study.

In Breast Cancer Research, Dr. Jenny Chang-Claude of the German Cancer Research Center, Heidelberg and colleagues note that VDR polymorphisms may influence cancer risk by altering the potentially anti-carcinogenic effects of vitamin D. Epidemiological studies have, however, previously yielded inconsistent results.

The researchers conducted a study of 1408 women with breast cancer and 2612 age-matched controls. They found no differences in serum 25-hydroxyvitamin D by VDR genotype. Overall, there was no association between the four individual polymorphisms analyzed and the risk of breast cancer.

What was interesting was that the Taql polymorphism was associated with the estrogen receptor status of tumours. Specifically, for t allele carriers compared to noncarriers among the breast cancer cases, the odds ratio was 1.18 for estrogen receptor-positive tumors and 0.88 for estrogen receptor-negative tumors.

Further analysis showed that the haplotype FtCA, which contains the Taql t allele, was associated with a significantly greater cancer risk (odds ratio, 1.43) than was FTCG, the most frequent haplotype.

It was concluded that the results support the potential effects of VDR polymorphisms on postmenopausal breast cancer risk. Future epidemiological studies assessing the association of vitamin D and breast cancer risk should therefore take the receptor status of the tumour and other gene variants of oestrogen metabolism into account.

Cancer research: blocking a gene may block cancer growth

Activating a cancer suppressor gene called nutlin-3a can block cancer cell division, according to researchers at the National Cancer Institute (NCI), part of the National Institutes of Health.

Nutlin-3a activates the p53 gene, leading to cellular senescence, a process by which cells lose their ability to grow and divide. An opportunity for new genetic mutations occurs each time a cell divides, therefore limiting the number of cell divisions in a cancer cell inhibits tumour progression. This study is published in the May 1, 2008, issue of Cancer Research.