Last week, I mentioned that I’d come across an interesting story about a jazz musician and noted writer in Britain, who released a recording of his work begun in 1973. Keith Shadwick was a professional musician in Australia at the time, and he, along with drummer Gary Norwell, had formed a band called Sun, with a few other musicians. The group released one album, but then broke up. Keith and Gary recorded several jazz tracks before going their separate ways, and Keith revived the project off and on, in the mid 1980s and again in 2005 when he was diagnosed with mesothelioma.

A British record label, Candid Records, agreed to release the CD, and Keith recruited a number of musicians to fill in the gaps on the tracks to finally see the project through. The CD was called Free Time, a name initally selected because the original tracks recorded in 1973-74 were done during a recording studio’s down time, when a friend who worked there was able to lend Keith and Gary the space. But the liner notes, penned by Keith to tell the story of how the recording came together, tend to more solemn reflection.

“Then suddenly completion is in front of you and there is no free time anymore,” he writes, and it’s easy to see the dual implication of a completed project and a completed life.

Keith passed away just as the CD was pressed, and it is unlikely he saw it in its final form.

The special edition release of Free Time is available only through the Candid Records web site, and is shipped from the UK. Cost is £9.99 plus shipping, which totals around $24 U.S. once you figure in the exchange rate. But all proceeds from the sales will go to Bart’s Mesothelioma Research, an organization in Britain dedicated to the treatment of mesothelioma.

I received my CD yesterday. Full of free-spirited modern jazz tunes highlighting Keith on saxophone, the CD is joyful and jamming and sometimes poignant. It is perhaps hardest to comprehend when mesothelioma steals the breath of those who create music, before it steals their life.

Thirty-four years after its original recording, Candid Records has released a jazz CD to honor the memory of noted British journalist and musician Keith Shadwick, with all proceeds from the sale going to Bart’s Mesothelioma Research, a charity based in the UK dedicated to studying the asbestos related disease.

Shadwick, who passed away from mesothelioma on July 28, 2008, was a respected journalist and author whose background as a jazz and rock musician in the 1970s led to a career focus on music and musicians. His credits include books on noted jazz musician Bill Evans, as well as Jimi Hendrix and Led Zeppelin. He also authored The Jazz & Blues Encyclopedia, the Guinness Guide to Classical Composers, and edited The Gramophone Good CD Guide. Additionally, he was a regular contributor to publications including Jazzwise magazine, The Independent and The Daily Mail.

According to an article published on All About Jazz.com, during his early 20s, Shadwick was a jazz and jazz/rock musician, playing saxophone, flute and piano. He was a founding member of the Sydney, Australia-based group, Sun, which released one self-titled album in 1972 before splitting up. In 1973 and 1974, the story reports, Shadwick and fellow Sun member, drummer Gary Norwell, recorded some jazz tracks with fellow musicians Justin McCoy and Robert Luckey when local Point Five Studio offered them use of its facility during a free downtime.

As a nod to their luck in securing the studio, the musicians named the album Free Time, but it was not completed or released. Shadwick held onto the tapes, and revived work on the recording in 1984, with guitarist Billy Jenkins, and again in 2005, with guitarist Mike Wollenberg.

All About Jazz notes that Shadwick was motivated to finish the album in 2005, when he was diagnosed with mesothelioma, and completed the project in 2007, although it is unlikely that he lived long enough to see its official pressing, which was delivered to his home right around the time of his death. The album was produced and released by Candid Records in the UK.

The Special Edition of the Free Time CD is available in limited release through the Candid Records web site, with all proceeds benefitting Bart’s Mesothelioma Research. Cost is £9.99 plus shipping, which totals around $24 U.S.

Today Alfacell, the manufacturer of ONCONASE, announced it will begin distribution of the mesothelioma drug in Israel. The company will partner with Megapharm, Ltd., a leading pharmaceutical company in Israel. ONCONASE recently completed an international confirmatory Phase IIIb clinical trial for unresectable malignant mesothelioma.

The news comes just a day after Haaretz.com, a leading news outlet in Israel, noted that asbestos-related cancer is 10 times more prevalent in Nahariya, a city of approximately 50,000 located in the North District of Israel on the Mediterranean sea, just south of the Lebanese border at Rosh HaNikra, than it is in the rest of the country. The report is based on data submitted by the chief doctor of the Health Ministry’s Acre District.

The medical report was presented to the Knesset Internal Affairs Committee, which is currently calling for greater action from Nahariya’s government to address the problem. The story quotes Tamar Bar On, head of the Environment Ministry’s Asbestos Department, as saying that “between 70 to 150 thousand cubic meters of asbestos [can] be found scattered across the Western Galilee, mainly in private yards.”

Committee MK Yossi Beilin (Meretz) has been selected by the committee to chair a panel dedicated to addressing the asbestos problem in Nahariya.

Alfacell will manufacture and supply ONCONASE to Megapharm, while Megapharm will be responsible for all activities and costs related to regulatory filings and commercial activities in a defined marketing territory, according to an Alfacell press release.

ONCONASE is a first-in-class therapeutic product candidate based on Alfacell’s proprietary ribonuclease (RNase) technology. A natural protein isolated from the leopard frog, ONCONASE has been shown in the laboratory and clinic to target cancer cells while sparing normal cells. ONCONASE triggers apoptosis, the natural death of cells, via multiple molecular mechanisms of action.

ONCONASE has been granted fast track status and orphan-drug designation for the treatment of malignant mesothelioma by the FDA. Additionally, ONCONASE has been granted orphan-drug designation in the European Union and Australia.

On April 21 I reported that a Madison, Wisconsin-based biotechnology firm, Quintessence Bioscience, was moving forward on a drug similar to Alfacel’s Onconase, to treat mesothelioma. The report, from Steve Clark for WTN (Wisconsin Technology Network) News, noted that the company’s QBI-139 is very similar to Onconase, but has not been clinically tested yet.

Of course, on Monday this week, it was announced and reported here that Onconase had failed the primary objective of its late-stage trial. This news was particularly disappointing since the drug already has orphan drug status in the U.S., Europe and Australia due to the very high hopes for its success. Despite failing in its primary objective, however, testing did show that the drug is effective in a secondary effect, helping to prolong the life of those treated after standard chemotherapy has failed.

The report of Onconase’s initial failure prompted WTN’s Clark to revisit Quintessence to find out if the Onconase failure would derail the development of their QBI-139. In his new report, Clarks says he found researchers undaunted and pressing forward. He says they hope to move the drug into clinical trials sometime this summer, and they believe the success of Onconase’s secondary role and hopeful FDA approval in that area will help pave the way for general acceptance of RNase cancer therapies.

In his earlier report, Clark pointed out that QBI-139 has several differences from Onconase in the way it is produced, which he believes will make it inherently more effective than Onconase.

He points out that mesothelioma is a particularly difficult cancer to treat, and wonders if the selection of mesothelioma as a research track by Alfacell was made to help fast-track the development of the drug. Perhaps, he wonders, the drug might be more effective on “more common and easier to treat cancers than mesothelioma.”

Alfacell Corp., a biotechnology company that manufactures Onconase, released a disappointing report Wednesday regaring its Onconase product, which was hoped to be a significant treatment for mesothelioma. The drug already has orphan-drug status for the treatment of malignant mesothelioma in the U.S., Europe and Australia.

Results of the company’s late-stage trial of the drug showed that Onconase did not achieve significantly higher survival rates among patients with unresectable malignant mesothelioma when given in combination with doxorubicin, another cancer chemotherapy drug.

According to a report on Pharmaceutical Online, the preliminary results are based on 320 evaluable events that occurred in the clinical trial out of a total of 428 patients randomized. The analysis of the data did not show a statistically significant improvement for evaluable patients receiving Onconase plus doxorubicin. The median survival time (MST) for evaluable patients who received Onconase plus doxorubicin was 11.1 months as compared to 10.7 months for patients who received doxorubicin as a single agent.

However, there is a silver lining to the study. Pharmaceutical Online reports those patients who failed a previous chemotherapy regimen who received Onconase plus doxorubicin experienced a MST of 10.5 months compared with 8.7 months for those patients who received doxorubicin, which is considered a statistically significant result.

Reuters reports as a result of this secondary finding, Alfacell will now submit a marketing application to the Food and Drug Administration for use of the drug on those patients, with hopes to have it approved by the end of the year.

A report in The Courier Mail, based in Queensland, Australia, says mesothelioma deaths could double in the coming years, as the disease begins to strike end users of asbestos products, like amateur home renovators.

According to the report, the “first wave” of mesothelioma victims were those who mined asbestos, and the second wave affected people who worked with asbestos in factories or manufacturing industries. The next wave, they say, is affecting people who work with asbestos materials, like construction workers.

In addition to mesothelioma, exposure to asbestos, which has been used in building materials in Australia for decades, also causes asbestosis and asbestos-related lung cancers.

Asbestos Diseases Foundation of Australia president Barry Robson is working with government officials for a national approach to education, treatment and compensation for asbestos-related diseases.

A new study is predicting 10 percent of Australian carpenters born before 1950 will die of mesothelioma.

The Australian study, conducted by cancer research specialist Professor Julian Peto, was based on research into the lifetime occupations of 600 mesothelioma patients. Its findings were reported by the web site news.theage.com.au yesterday.

Peto predicts 30,000 Australians will die from mesothelioma between 2000 and 2050. He says the cause is exposure to both crocidolite asbestos (blue asbestos) and amosite (brown asbestos), which was used in building products in Australia and Britain until the 1980s.

According to the story on theage.com.au, Peto’s research reveals that Australia and the UK currently have the highest rates of mesothelioma in the world, with an estimated 600 cases per year in Australia and 2,000 in Britain, with numbers still rising.

Because I write this blog in the United States, I don’t talk as much about the looming global disaster asbestos poses. But it’s frightening, and it’s sickening, to see the effects of asbestos exposure just surfacing in communities around the world. I am afraid the coming suffering is unimaginable.

I recently posted about the progress of a new drug to treat mesothelioma, called ONCONASE, which has completed Phase IIIb clinical trials and is being fast-tracked for approval in the U.S. ONCONASE already has orphan-drug status in the EU and Australia.

This week, I found a story that provides even more hope. It seems a Madison, Wisconsin-based biotech firm, Quintessence Bioscience, also has a promising mesothelioma drug in the works that operates along the same lines as ONCONASE, tagged QBI-139. The Quintessence drug is not yet in clinical trials.

Both drugs target RNA in cancer cells. They are therapeutic ribonucleases (RNases), which WTN News (Wisconsin Technology News) writer Steve Clark describes as “ubiquitous enzymes that destroy RNA.” He explains that researchers including the University of Wisconsin-Madison’s Ronald Raines, “discovered that RNases from non-human species sometimes are not regulated inside human cells and can cause cell death. Surprisingly, cancer cells are much more susceptible than normal cells to foreign RNases.”

The ONCONASE product is made from purified frog eggs. The Quintessence drug is 95 percent human, but still kills human cancer cells, Clark reports. Both drugs can kill a wide range of different human cancer types, he says, so its application has broad potential. The ONCONASE clinical trial data is from patients with malignant mesothelioma.

Clark reports that Quintessence is optimistic about its QBI-139 surpassing the positive results of ONCONASE. He says that frog-derived ONCONASE has been shown to cause allergic reactions in some patients, which would be mitigated in the 95 percent human-gene QBI-139. Additionally, he reports QBI-139 is less toxic than ONCONASE, which will allow it to be better tolerated by some patients in larger doses.

Currently, Clark reports, QBI-139 is being produced for use in a Phase I clinical trial, which is set to begin this summer and end sometime in 2009. It is anticipated that the trial will be held at the University of Wisconsin Carbone Cancer Center.

Read the full article at WTN News.

Steve Clark, Ph.D., is a former professor and medical researcher at the University of Wisconsin School of Medicine and Public Health, and is currently a freelance writer and consultant on biotechnology issues.

SOMERSET, N.J., April 2, 2008 - PRNewswire - Alfacell Corporation today announced that it has confirmed that 316 evaluable events (patient deaths) have occured in the confirmatory Phase IIIb clinical trial of its lead compound, ONCONASE (ranpirnase), for the treatment of patients with unresectable malignant mesothelioma (UMM).

In accordance with the statistical plan for the trial, the company has begun the process necessary to conduct the formal statistical analyses required to complete the final sections of the ONCONASE rolling New Drug Application (NDA).

The trial was designed to show a statistically significant improvement in overall survival for UMM patients who were treated with a combination of ONCONASE and doxorubicin as compared to UMM patients who were treated with doxorubicin as a single agent. Enrollment in the ONCONASE Phase IIIb clinical trial closed on Sept. 30, 2007. A total of 428 patients were enrolled in the trial.

Alfacell has licensed the U.S. commercial rights for ONCONASE to Strativa, the branded product division of Par Pharmaceuticals, Inc. Strategic marketing and distribution agreements for ONCONASE have been secured with BL&H Co. Ltd. for Korea, Taiwan and Hong Kong, USP Pharma Spolka Z.O.O., an affiliate of US Pharmacia, for Eastern Europe, and GENESIS Pharma, S.A. for Southeastern Europe.

ONCONASE has been granted fast track status and orphan-drug designation for the treatment of malignant mesothelioma by the U.S. Food and Drug Administration (FDA). Additionally, ONCONASE has been granted orphan-drug designation in the European Union and Australia.

A Melbourne, Australia-based drug manufacturer, Cytopia Limited, is proceeding to the next phases of testing in clinical studies for its anti-cancer compound, CYT997.

The vascular disrupting agent (VDA) is under investigation in treating specific types of cancer with high unmet medical need and poor prognosis. Mesothelioma is included in the study, and is entering Phase II clinical trials.

The company reports favorable findings in mesothelioma patients in a Phase I trial. Based on these results, Cytopia is beginning feasibility analysis for a Phase II study in mesothelioma patients who have failed the currently approved drug, Alimta (pemetrexed).

The single-arm study will include 20-30 patients in Australia, the United States and Asia. The company hopes that activity in second-line mesothelioma could lead to expedited drug approval and a fast to-market strategy for the compound in this cancer indication. They expect to file reports on this study in the third quarter of 2008.

Cytopia, Ltd., is an Australian biotechnology company focused on the discovery and development of new drugs to treat cancer.