Pharma Buzzword Bingo

By MaverickNY on April 17, 2010

After listening to a lot of analyst and Q1 webcasts from Pharmaland lately, I have to groan at the lack of imagination shown across the board. Those waterfall slides, so beloved of senior management with a junior management consultant or intern on their team, drive me potty. It's always the same story… a few upsides here, a few glitches there, oh and here's our new number. Marketing fluff and puff, sigh.

That said, the delightful Tom Fishburne cracked me up this morning with his cartoon:

Source: Tom Fishburne

Thus I'm glad to be heading off to DC today and relative purity of scientific cancer research at the annual American Association of Cancer Research (AACR) meeting. Expect a deluge of posts of the next few days on hot research topics I find interesting!

Managing Multiple Myeloma: turning an acute cancer into a chronic disease

By MaverickNY on April 16, 2010

The other day while travelling home on a long train journey, I was browsing the NY Times app on my iPhone and came across an interesting story about multiple myeloma in the Health section:

"For many patients with cancers like chronic lymphoma, chronic myelocytic leukemia and now multiple myeloma, longevity lies in the ability of science to remain one step ahead of the malignancy by unraveling its genetic and molecular underpinnings and producing treatments tailored to counter them."

Now, I don't think there is actually something called chronic lymphoma (non-Hodgkins lymphoma (NHL), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML), yes), but you get the gist of what the reporter is saying – acute deadly hematologic cancers are gradually being turned into chronic diseases.

The main reasons behind this are several fold:

Greater understanding of the science and biology underlying the diseases.
Increased number of available therapies that can be sequenced, prolonging overall survival.
Move from chemotherapy to more targeted therapies, improving quality of life.
Active drug pipeline in myeloma across several companies, offering increased hope for further advancements in the disease as new combinations evolve.
Updating of treatment guidelines and new standards (e.g. see this Myeloma example)

In addition, the growth of Myeloma support groups has provided a wealth of online information, practical advice, and emotional support for people suffering with the disease. Some great resources include:

Multiple Myeloma Research Foundation (run by an incredible myeloma survivor, Kathy Giusti)
International Myeloma Foundation
Leukemia and Lymphoma Society
National Organisation of Rare Diseases
American Cancer Society

In addition, Pharma companies such as Millennium, Celgene and Onyx/Proteolix are also doing their bit to improve research and outcomes in multiple myeloma in R&D, and some provide people with balanced and fair disease information – not everything has to be promotional. One such example is an unbranded site about Myeloma supported by Millennium-Takeda, the manufacturers of bortezomib (Velcade) called My Multiple Myeloma. Velcade is a proteasome inhibitor that has become the cornerstone of front-line therapy either without or before a stem cell transplant.

Now, let's take a look at the My Multiple Myeloma website. I should disclose here that the agency who are responsible for building the site are a client, although I wasn't involved in the website project itself. I've long had an interest in unbranded sites and disease information from my marketing days, so let's look at what's available at the moment.

The opening site page offers some sensible choices with clear navigation encouraging people to take charge of their disease and some shots of real people who are experiencing multiple myeloma, you can click through and read more about their stories and experiences:

One of the things that many people forget is that cancer is a complex disease, not only in terms of treatment options, but all the other factors that need to be considered. Googling for information can be overwhelming and none of the current advocacy sites offer a one-stop shop for everything. The site looks to reduce this overload and provide a central starting repository for information. Further into My Multiple Myeloma, you can find some other interesting and relevant information such as coping with the disease, working with the health care professionals involved, costs and insurance, understanding emotions, lifestyle advice, and where to find clinical trials for example:

It will be interesting to see how the site evolves over time and hopefully adds useful tools to allow people to engage and share information with each other. Providing relevant information is a good start, albeit a static one, but allowing interactivity and sharing of ideas will help bond those affected even more.

It would be cool to add other practical things such as a wiki for transplant centers, contacts, and other academic centers specialising in the treatment of myeloma, for example. That way, people can find a hospital near them, or even a means of finding local support groups perhaps.

In the past, I have seen significant value in watching patients converse, help and support each other in disease forums because many-to-many is so much more powerful and effective than an isolated n of 1. People need to feel that they are not alone in their fight against cancer, having a sense of support and community really does help mobilise heart and desire to beat the disease.

It always annoys me when people think Pharma companies are only interested in promotional or DTC programs that make money or add ROI; in oncology and hematology, I've yet to meet someone from the industry who didn't care about people, improving survival and outcomes or making a difference to people's lives.

Maybe cancer is just a different world… after all, we have very few placebo controlled trials in this arena; new therapies and combinations typically go head to head against the standard of care in a survival of the fittest approach. May the best ones win and make a difference, which is great news for people suffering from any cancer.

Hope is one thing, but improved outcomes and information are even better.

Kumar, S., Mikhael, J., Buadi, F., Dingli, D., Dispenzieri, A., Fonseca, R., Gertz, M., Greipp, P., Hayman, S., Kyle, R., Lacy, M., Lust, J., Reeder, C., Roy, V., Russell, S., Short, K., Stewart, A., Witzig, T., Zeldenrust, S., Dalton, R., Rajkumar, S., & Bergsagel, P. (2009). Management of Newly Diagnosed Symptomatic Multiple Myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines Mayo Clinic Proceedings, 84 (12), 1095-1110 DOI: 10.4065/mcp.2009.0603

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New developments in castration resistant prostate cancer – MDV3100

By MaverickNY on April 15, 2010

Last night I received an alert from Medivation announcing that an article would be published in today's online The Lancet regarding their prostate cancer agent, MDV3100. Sure enough, here's the article:

Although the trial is an early phase I/II study, encouraging antitumour effects were reported in 140 men, of whom 65 were chemotherapy naïve. Time to disease progression (TTP) was 47 weeks, which is decent considering the men in the study were all castration resistant and likely had advanced disease.

Obviously, it is too early to tell yet quite what Medivation and Astellas have here, but to put things in context, docetaxel (Taxotere), was approved for hormone refractory prostate cancer (HRPC) with prednisone in androgen independent (hormone refractory) metastatic prostate cancer with a median overall survival of 18.9 months (approx. 85 weeks) in a large phase III trial.

We must also remember that in another more recent trial, it was demonstrated that men who received cabazitaxel (sanofi-aventis' follow on taxane to docetaxel) lived a median of 15.1 months (68 weeks), compared with 12.7 months (57 weeks) for those who receive mitoxantrone, a difference that was statistically significant.

That said, the side effect profile of chemotherapy is certainly not benign, with significant risk of myelosuppression and infectious complications.

However, what was encouraging about the Medivation trial was early Kaplan Meier response curves, which demonstrated those men who had no previous chemotherapy generally did better than those who received it in terms of both PSA and radiological progression.

At the AACR Molecular Targets meeting last November, Charles Sawyers gave a keynote talk on prostate cancer and looked at the various opportunities for investigating new therapeutics in clinical trials for prostate cancer. He suggested that circulating tumour cells (CTCs) might be a more useful marker for disease status than PSA. In The Lancet study, the authors noted that:

"We recorded early post-treatment conversions from unfavourable to favourable in 75% of patients not exposed to chemotherapy and in 37% of those who were exposed. Decreases in PSA were generally associated with parallel falls (or no progression) in CTCs, but this finding was not consistent, suggesting that these measures assess different aspects of the malignant process. PSA decreases might in some cases be an indicator of the mechanism of action of MDV3100 as an androgen-receptor antagonist rather than an actual antitumour effect. However, the benefit of MDV3100 on several assessments, including CTCs and radiological time to progression, suggest that MDV3100 does have a true antitumour effect."

The other interesting observation that Sawyers made was that traditionally, early prostate disease is treated with oral hormonal therapies and once castration resistance sets in, the patient is referred to an oncologist for consideration of chemotherapeutic options. With the advent of new therapies with different MOAs in development such as MDV3100, abiraterone (Cougar/J&J) and Provenge (Dendreon), the lives of men with prostate cancer can potentially be extended further before stage IV metastases sets in.

At AACR last November, Sawyers also discussed the importance of androgen receptor signalling in the disease (previously discussed here with simple models) and the data from this trial seem to bear out his elegant theory. I'd like to see more analysis though and learn whether those men who had AR amplified prostate cancer did better on MDV3100 than those who did not?

All in all, this is an exciting time for men with prostate cancer. Dendreon's Provenge may well be the first new drug that fits between the hormonal therapies and chemotherapy, since the FDA PDUFA date is May 1st, although since that is a Saturday, we may well here the Go/No Go news on Friday 30th April.

In the meantime, the annual AACR meeting in DC this weekend can't come soon enough!

Scher, H., Beer, T., Higano, C., Anand, A., Taplin, M., Efstathiou, E., Rathkopf, D., Shelkey, J., Yu, E., & Alumkal, J. (2010). Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study The Lancet DOI: 10.1016/S0140-6736(10)60172-9

The molecular genetics of aggressive B-cell lymphomas

By MaverickNY on April 15, 2010

As many readers here on PSB know, I've not been a big fan of genome-wide molecular profiling, preferring an oncogene addiction approach to drug development and targeted cancer therapies. However, every once in a while something comes along that stops you in your tracks and makes you think differently.

This morning I was reading the latest copy of the New England Journal of Medicine over coffee and was fascinated by a review article by Drs Lenz and Staudt at the NCI on the molecular genetics of diffuse large-B-cell lymphomas (DLBCL), which account for 30-40% of newly diagnosed lymphomas.

As the review article points out, it is well know that different subsets of diffuse large-b-cell lymphomas are associated with different overall survival rates after initial anthracycline based therapy. For example, it is more favourable in people with PMBL and the GCB subytype but less favourable in those with the ABC subtype. R-CHOP therapy has improved survival in people with ABC, but the cure rates are still lower than those with the GCB subtype. Gene expression signatures can help identify the subtypes and predict survival rates:

Source: NEJM

Current therapeutic treatment with chemotherapy has made headway in improved survival, but in order to make further headway, new approaches are very much needed. Targeted therapies have now begun to expand clinical trial options.

The article talks about numerous pathways, but I particularly liked this one, which details the Nuclear Factor kB (NFkB) signalling pathways in normal and malignant lymphocytes:

Source: NEJM

Essentially, signalling is initiated when a SRC family kinase ( SFK) phosphorylates tyrosines in the immunoreceptor tyrosine-based activation motifs (ITAMs) on B-cell subunits. SYK is then recruited to the ITAMs through the SH2 domains and becomes active. Many of you will remember SYK inhibition from previous posts on Rigel's fostamatinib, a SYK inhibitor. I think Celgene also mentioned a SYK inhibitor in early development at their recent R&D Day, although the Rigel-AZ is further ahead but more erratic in it's results, at least in immune disorders. A more recent paper in Blood looked promising in NHL and CLL, though. Companies are clearly starting to look at specific inhibitors in the downstream pathway for lymphomas and chronic lymphocytic leukemia.

What's interesting about the cartoon above is that you can also see that phosphatidylinositol-3-kinase (PI3-kinase) is activated in parallel, activating the mTOR pathway. These two targets are getting a lot of attention from Pharma in the clinic, especially in leukemias and lymphomas, and we may well see more of their latest development at AACR next week and ASCO in June. Exelixis and their partner, sanofi-aventis (a client), for example, have already announced 12 abstracts at ASCO, including 6 on their PI3K and mTOR inhibitors, but they are focusing on lung cancer, a much more difficult carcinoma, rather than NHL, where there is a strong rationale.

It's good see new treatment modalities being tested in leukemias and lymphomas and not just solid tumours, where most companies inevitably focus due to the larger population sizes. That said, the challenge in lymphoma is going to be identifying rational combinations that kill lymphoma cells synergistically. As we learn more about the underlying biology of the disease, targets and biomarkers, so more effective and less toxic solutions may evolve.

Lenz, G., & Staudt, L. (2010). Aggressive Lymphomas New England Journal of Medicine, 362 (15), 1417-1429 DOI: 10.1056/NEJMra0807082

Friedberg, J., Sharman, J., Sweetenham, J., Johnston, P., Vose, J., LaCasce, A., Schaefer-Cutillo, J., De Vos, S., Sinha, R., Leonard, J., Cripe, L., Gregory, S., Sterba, M., Lowe, A., Levy, R., & Shipp, M. (2009). Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia Blood, 115 (13), 2578-2585 DOI: 10.1182/blood-2009-08-236471

Using technology to derive Sentiments Analysis in Pharma

By MaverickNY on April 14, 2010

This week offers a nice break in science topics on the blog and a chance to look at how technology can be used to monitor social media, physician and patient sentiments about drugs and various diseases in a practical way. I've been interested in analysing trends in data since my undergraduate days when I created the first automated computerised football (soccer) notation system for looking at strategies and tactics employed by winning and losing teams.

There's a LOT of blah blah talk about social media out there, in particular from self styled gurus and experts, which tends to make me tune out for the most part. In my spare time (away from being immersed in preclinical and clinical data), what I'm really interested in is how mathematical algorithms can be applied to speech and words using modern computer techniques to extract feeling, tone and meaning from sentiments in meaningful ways.

After yesterday's 5 minute Lightening Talk at the Sentiments Analysis Symposium in New York hosted by Seth Grimes of Alta Plana, I received a few requests for the presentation, entitled "Next generation sentiment extraction: light at the end of the tunnel, but will it negate the need for human supervision?"

So here it is for those interested:

Using Sentiment Analysis in Pharma and Biotech

View more presentations from maverickny.

The file is downloadable and I'm pleased to say that the quality is much better than reading it in Slideshare online, which may look a little fuzzy.

I managed to do the brief presentation with 10 seconds to spare. There nothing worse than getting half way through and the buzzer goes before you get to the interesting bits!

If anyone wants any further information, please feel free to contact me. We have several interesting projects ongoing with sentiments analysis in oncology at the moment.

Next week normal service will resume and I will be busy reporting on hot science and research topics at the American Association of Cancer Research Meeting in DC, as they have kindly offered Pharma Strategy Blog a science blogger pass and an opportunity to bring new developments in science and cancer biology to life here. Watch this space!

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Sentiments Analysis in Pharma

By MaverickNY on April 13, 2010

It's turning out to be a busy week already. After two days in Boston, today I'm off to the Sentiments Analysis Symposium in New York, where I'm presenting a lighting 5 minute talk on sentiments analysis in Pharma.

We've been working on some cool tools in our spare time and have started rolling out some analysis in different cancer types such as renal cell and sarcoma as the first examples using an automatic sentiment lens. The presentation today will look at an immune disorder, Lupus, as an example. The technology is something we're very excited about and look forward to posting about this as it evolves.

Oddly, I've discovered that it took longer and more effort to condense some thoughts and ideas simply into a 5 minute vignette than it does for a 30 minute presentation!

The meeting is being held at the Executive Conference Center in Midtown at 1601 Broadway, so do stop by if you're interested in this fascinating area.

The potential for PI3K pathway inhibitors in lung cancer

By MaverickNY on April 12, 2010

Life is about stories, events and even coming back full circle sometimes. I experienced that moment of déjà vu this morning on opening a link to an article that a colleague kindly sent from Avrum Spira’s lab that was published in Science Translational Medicine, simply titled:

Airway PI3K Pathway Activation Is an Early and Reversible Event in Lung Cancer Development

Many moons ago I completed my doctoral thesis on the early detection of lung disease at King’s College London. Much of it was about the impact of smoking on the airways. Halfway through the 3 year MRC grant, while listening to some evening lectures at the Brompton Hospital by Prof Peter Barnes and Steven Holgate, I realised that the real answer lay in understanding the biochemical and molecular biology pathways… only we were working on the physiology of breathing patterns. An a-ha moment to be sure.

Still, I was able to pick up differences in breathing patterns between healthy non-smokers and those who were medium to heavy smokers.

The unaswered question, though, was why?

Prof Barnes loved to put up charts of pathways with a black background and different targets meticulously coded with coloured highlighter pens… PDE, leukotrienes, cholinergic mast cell activation and many others sprang to life as he walked students through the various possible mechanisms where pharmaceutic intervention might have a role to play.

Fourteen years on, I don’t think a cure for asthma has been found and many of those pathways have not yielded much in chronic obstructive pulmonary disorder (COPD) either, except perhaps anti-cholinergics such as tiotropium bromide (Spiriva) as maintenance therapy in controlling bronchospasm. My suspicion at the time was that the mechanisms underlying inflammation and aggravation of the airways by chemicals was key to unlocking why some people get lung cancer, others COPD and still others were unaffected.

Fast forward to the article.

Last week, Gustafson et al., published a paper in Science Translational Medicine suggesting that phosphatidlyinositol 3-kinase (PI3K) pathway activation is an early event in the development of lung cancer.

In particular, they found elevated PI3K in the airways of smokers with lung cancer compared to smokers without lung cancer:

Source: Science Translational Medicine

The researchers validated their hypothesis that activation of PI3K is an early event in the development of lung cancer by comparing the cytology of airway epithelium from healthy smokers to those with mild to moderate airway dysplasia that reflects an early noncancerous abnormality, often considered a precancerous state. The theory being that if smokers with dysplasia have higher PI3K pathway activation then this would suggest P13K pathway activation precedes the development of lung cancer.

The results showed increased expression of genes induced by PI3K pathway in high risk smokers and those with lung cancer. This may well explain the dysplasia and inflammation seen, which you can see in the chart below:

Source: Science Translational Medicine

One key question this research raises, but does not answer, is whether P13K pathway inhibitors have a role to play in the treatment of lung cancer?

Thinking about my doctoral research on early detection of lung disease, this statement made me sit up and pay attention:

“These results suggest that deregulation of the PI3K pathway in the bronchial airway epithelium of smokers is an early, measurable, and reversible event in the development of lung cancer and that genomic profiling of these relatively accessible airway cells may enable personalized approaches to chemoprevention and therapy.”

Whoa! Early detection of lung cancer?

Forgive my excitement and enthusiasm, but it’s kind of cool to see read that scientists can actually find something biochemically active that may represent a new target for intervention fifteen years after you realise that early detection might be possible, if only you knew what the target might be. That’s the stuff of <goosebumps.

PI3-kinase is a fascinating target that quite a few biotech and pharma companies are looking at as a potential mechanism for the treatment of cancer. I’ve written and blogged extensively on this (see here, here, here, here and here) for some examples.

Interestingly, many of the PI3-kinase compounds in early clinical development are investigating the agents in leukemias, lymphomas, breast, ovarian and gastric cancer or basket solid tumour trials. Some of the interesting small biotech companies in this field include Calistoga, Semafore and Exelixis and big pharma is represented by Merck, Novartis, sanofi-aventis and Roche. Only two agents seem to be specifically looking at non-small cell lung cancer (NSCLC) though – no prizes for guessing which ones:

Everolimus (Novartis), a combined mTOR-PI3 kinase inhibitor, in phase II development.
GDC-0941 (Roche/Genentech), which is looking at whether the new agent adds anything to the current standard of care in NSCLC ie carboplatin + paclitaxel + bevacizumab and is currently recruiting patients.

Novartis (a client) have completed their trial according to the clinical trials database, so it will be interesting to see if there are any data at ASCO in June that will help us learn more about the disease.

If the data from the Novartis or Roche trials are positive, the companies may be very interested to read Gustafson et al.’s suggestion:

“Our work further suggests that additional lung cancer chemoprevention trials either targeting the PI3K pathway or measuring airway PI3K activation as an intermediate endpoint are warranted.”

Chemoprevention is a big word in cancer research.

In two weeks time, I’ll be at the AACR annual meeting in DC (do let me know if you are going and would like to meet up for a coffee and chat) and hopefully there will be more about this fascinating pathway then. Watch this space!

Gustafson, A., Soldi, R., Anderlind, C., Scholand, M., Qian, J., Zhang, X., Cooper, K., Walker, D., McWilliams, A., Liu, G., Szabo, E., Brody, J., Massion, P., Lenburg, M., Lam, S., Bild, A., & Spira, A. (2010). Airway PI3K Pathway Activation Is an Early and Reversible Event in Lung Cancer Development Science Translational Medicine, 2 (26), 26-26 DOI: 10.1126/scitranslmed.3000251

3 Comments

Update on Multiple Myeloma: are molecular remissions possible without a transplant?

By MaverickNY on April 8, 2010

By strange coincidence this morning I was listening in to the Celgene R&D Day presentations including an update on their plans for their iMiD therapies thalidomide (Thalomid) and lenalidomide (Revlimid), while reading a couple of interesting papers about Millennium-Takeda's bortezomib (Velcade) that were just published in the Journal of Clinical Oncology last month and another this week for the treatment of multiple myeloma. All three of these drugs have changed the treatment of multiple myeloma from a certain death sentence to a treatable disease.

I'll post more about the Celgene pipeline in a later post, but the papers are well worth sharing and discussing. One report looked at the phase III data for the VISTA (Velcade as Initial Standard Therapy in Multiple Myeloma) trial. This study was presented at the recent American Society of Hematology (ASH) meeting in December (see previous post), but the paper now includes updated survival data in a large cohort of 682 people:

"With a median follow-up of 36.7 months, there was a 35% reduced risk of death with VMP versus MP (hazard ratio, 0.653; P < .001); median OS was not reached with VMP versus 43 months with MP; 3-year OS rates were 68.5% versus 54.0%. Response rates to subsequent thalidomide (41% v 53%) and lenalidomide based therapies (59% v 52%) appeared similar after VMP or MP; response rates to subsequent bortezomib-based therapy were 47% versus 59%.

Among patients treated with VMP (n = 178) and MP (n = 233), median survival from start of subsequent therapy was 30.2 and 21.9 months, respectively, and there was no difference in survival from salvage among patients who received subsequent bortezomib, thalidomide, or lenalidomide. Rates of adverse events were higher with VMP versus MP during cycles 1 to 4, but similar during cycles 5 to 9. With VMP, 79% of peripheral neuropathy events improved within a median of 1.9 months; 60% completely resolved within a median of 5.7 months."

The bold for emphasise is mine, but anytime you see a greater than 30% reduced risk of death from a treatment, one is bound to sit up and take notice, especially if you have a loved one suffering from the disease.

What do these results mean? Well, in practice they clearly demonstrate that VMP significantly prolongs OS versus MP after lengthy follow-up and extensive subsequent therapy for myeloma. What was particularly encouraging is that first-line bortezomib use does not induce more resistant relapse, which is also important for people sufffering from the disease.

The combination of VMP used upfront therefore appears more beneficial than first treating with conventional agents such as melphalan and prednisone and saving bortezomib and other novel therapies until relapse. Historically, oncologists often leave the big guns in their back pocket, but the data from this trial may well change their thinking about treatment strategies in multiple myeloma, at least.

The second paper examined the effect on minimal residual disease, by qualitative and real-time quantitative polymerase chain reaction (RQ-PCR), of a consolidation regimen that included the combination of bortezomib (Velcade), thalidomide (Thalomid), and dexamethasone (VTD) in people with multiple myeloma who responded to autologous stem-cell transplantation (auto-SCT). Although the results are more preliminary – this was a phase II trial with only a small number of patients (n=39) – they are very encouraging indeed.

This study is particularly important because it may be the first to document the occurrence of persistent molecular remissions (almost undetectable disease) in a proportion of people with multiple myeloma treated without allogeneic transplantation. To put this is context, until now, a transplant was the only known curative treatment that has been shown to induce molecular remission, so to achieve that state with therapy alone is something that will give many people goosebumps.

Why?

Because SCT are associated with 20% treatment related mortality alone, so if that number can be reduced by excluding the risk of death, then it offers hope not just for those who are ineligible for a transplant, but as another option for those who are.

The researchers also noted that:

"The major reduction in tumor load recorded by RQ-PCR after VTD suggests that unprecedented levels of tumor cell reduction can be achieved in MM thanks to the new nonchemotherapeutic drugs."

That's all sorts of awesome news, albeit in a small study, but it does augur well for the future if the results can be repeated in a phase III study.

Ladetto, M., Pagliano, G., Ferrero, S., Cavallo, F., Drandi, D., Santo, L., Crippa, C., De Rosa, L., Pregno, P., Grasso, M., Liberati, A., Caravita, T., Pisani, F., Guglielmelli, T., Callea, V., Musto, P., Cangialosi, C., Passera, R., Boccadoro, M., & Palumbo, A. (2010). Major Tumor Shrinking and Persistent Molecular Remissions After Consolidation With Bortezomib, Thalidomide, and Dexamethasone in Patients With Autografted Myeloma Journal of Clinical Oncology DOI: 10.1200/JCO.2009.23.7172

Mateos, M., Richardson, P., Schlag, R., Khuageva, N., Dimopoulos, M., Shpilberg, O., Kropff, M., Spicka, I., Petrucci, M., Palumbo, A., Samoilova, O., Dmoszynska, A., Abdulkadyrov, K., Schots, R., Jiang, B., Esseltine, D., Liu, K., Cakana, A., van de Velde, H., & San Miguel, J. (2010). Bortezomib Plus Melphalan and Prednisone Compared With Melphalan and Prednisone in Previously Untreated Multiple Myeloma: Updated Follow-Up and Impact of Subsequent Therapy in the Phase III VISTA Trial Journal of Clinical Oncology DOI: 10.1200/JCO.2009.26.0638

Improved survival in a rare cancer with chemotherapy

By MaverickNY on April 8, 2010

An interesting article has been published in the latest New England journal describing how the addition of a cisplatin to gemcitabine improved survival by two months in biliary tract cancer. Currently, there is no standard treatment for this rare disease, so a solid phase III trial (ABC-02) represents an important step forward for treatment.

Biliary tract cancers are tumours that develop in the gallbladder and bile ducts. Those that develop in the bile duct within the liver are known as cholangiocarcinomas. Approx. 6500 new cases of gallbladder carcinoma are diagnosed each year in the US. Interestingly, chronic inflammation appears to be a common aetiologic factor in the disease development. There has been a rise in incidence of the cancer in recent years, which may possibly be attributable to the association between liver disease and increasing hepatitis C virus infections.

Although there are no standards, gemcitabine has been the bedrock of palliation therapy for the disease based on the experience in pancreatic cancer. The earlier ABC-01 phase II trial suggested a benefit in adding a platinum to gemcitabine.

In the current ABC-02 phase III trial, the median overall survival with the combination was 11.7 months and 8.1 months in the gemcitabine alone group, a significant improvement of 3.6 months.

As a result, the combination of cisplatin and gemcitabine is likely to become the new standard of care for the treatment of biliary tract cancer. As we learn more about the science and biology underlying the disease, further improvements may be possible with the addition of targeted agents.

Reference

Valle, J., Wasan, H., Palmer, D., Cunningham, D., Anthoney, A., Maraveyas, A., Madhusudan, S., Iveson, T., Hughes, S., Pereira, S., Roughton, M., Bridgewater, J., & , . (2010). Cisplatin plus Gemcitabine versus Gemcitabine for Biliary Tract Cancer New England Journal of Medicine, 362 (14), 1273-1281 DOI: 10.1056/NEJMoa0908721

West, J., Wood, H., Logan, R., Quinn, M., & Aithal, G. (2006). Trends in the incidence of primary liver and biliary tract cancers in England and Wales 1971–2001 British Journal of Cancer, 94 (11), 1751-1758 DOI: 10.1038/sj.bjc.6603127

El-Serag HB, Engels EA, Landgren O, Chiao E, Henderson L, Amaratunge HC, & Giordano TP (2009). Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U.S. veterans. Hepatology (Baltimore, Md.), 49 (1), 116-23 PMID: 19085911

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Are you a crazy deranged fool (CDF)?

By MaverickNY on April 7, 2010

The other week someone asked me why I do so much work specialising in oncology and cancer, which admittedly can sometimes bring more sad news than good.

I answered simply: "because I'm a crazy deranged fool!"

Source: Hugh

I follow Hugh MacLeod's cartoons daily and also subscribe to his excellent newsletter. On bad days he keeps me sane, on good days I laugh out loud.

What on earth is a 'crazy deranged fool' you may be wondering?

According to Hugh:

"A CDF is my term for somebody like me, i.e. somebody who actually has the temerity to TRY to do what he loves for a living, as opposed to shlepping for his daily crust."

Running a consulting business and going to many scientific and cancer meetings has it's benefits – one of them is realising you're getting paid for doing something you love and have a lot of enthusiasm for.

Making sense of data is fun; finding patterns and trends amongst a mass of information on a huge variety of different cancers is sometimes like unravelling DNA.

Are you a crazy deranged fool?