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Aggregating the EHA 2010 tweets

By on June 8, 2010

After the success of the American Society of Clinical Oncology (ASCO) Twitter aggregation, with over 250 readers over the course of the weekend, I thought it would be fun to repeat the experiment for the European Hematology Association (EHA) meeting in Barcelona this weekend.  The tweet volume is likely to be significantly less tough, with fewer people tweeting from the event.

Most of the topics I'm interested in will be on leukemias, lymphomas and myeloma, so if you are interested in these cancers, you can follow the feed below.  I've aggregated two hashtags, #EHA10 and #EHA2010. 

Additionally, Dr Anas Younes from MD Anderson Cancer Center will also be attending and following his tweet stream may also be instructive, especially if you are interested in his specialty, lymphomas.

Do feel free to join in remotely in the back channel and add links, comments or ask questions if you feel so inclined. The more the merrier!

I'm particularly looking forward to the Patient Advocacy symposium chaired by Jan Geissler, an awesome guy who just happens to have CML.  While the science and clinical data are important, it's also critical to hear and learn from the advocacy viewpoint.  

On the healthcare (#hcsmeu) front, I'm also hoping to meet fellow Twitter buddies, Miguel and Angel for an impromptu tweetup of #hcsmeuES.  If you're on Twitter and interested in healthcare, check them all out, all three are great gentlemen I would highly recommend!

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#AUA2010: The beginning of a new era for prostate cancer?

By on May 30, 2010

Past American Urological Association (AUA) meetings have seen a lot of same old, same old with very little that is new in the way of truly innovative and exciting new developments.  In many ways, prostate cancer is the male equivalent of ovarian cancer, with pharma companies considering it after the breast, lung and colorectal cancers, despite prostate cancer being fairly large in terms in epidemiology, from a pure numbers perspective.

Why is this?

Firstly, we need to consider the natural course of the disease, which unlike breast and lung cancers, is fairly indolent.  Men diagnosed early with prostate cancer can live for 10-15 years, often with long periods of watchful waiting, making adjuvant trials necessarily long ones.

Secondly, once hormonal therapy begins to enable castration and reduction in the levels of testosterone that drives the cancer's growth, patients are seen and managed by urologists, who prefer to treat with oral therapies.  Until recently, Pharma focused very much on intravenous infusions designed for oncologists and never the twain really met in the middle.

Thirdly, traditional drug development for chemotherapy begins in the latest stage of treatment after failure of existing therapies (typically 2nd or 3rd+ line) and moves earlier up the disease stage in a classic niche by niche development strategy.

These factors combine to essentially create 3 distinct, albeit crude, phases of treatment for prostate cancer:

  1. Watchful waiting
  2. Androgen deprivation therapy (ADT)
  3. Chemotherapy for stage IV metastatic disease

How are things changing?

Dendreon recently received approval for their autologous cell vaccine, sipuleucel-T (Provenge) in asymptomatic metastatic castration resistant disease, meaning that in men where hormonal therapies cease to work but have some early evidence of metastatic disease, now have a completely new and relatively non-toxic therapeutic option prior to chemotherapy with Taxotere, mitoxantrone or even prednisone.

Much has been written about the potential for vaccines earlier in the disease when the tumour burden is much lower, so hopefully we will see some future exploration in this area now that the proof of concept for the first commercial cancer vaccine exists and Dendreon will have more funds to reinvest in R&D as revenues are generated.  They have a real opportunity here.

Past studies with docetaxel (Taxotere) have shown an improved survival benefit of 2.4 months over prednisone alone in androgen independent (hormone refractory) population that was essentially symptomatic.  Two phase III Provenge studies reported a median survival benefit of 4.1 and 4.5 months respectively, meaning that 50% of the men did better and 50% did worse than 4-4.5 months. 

There are now at least 8 other compounds in phase III development for the treatment of advanced prostate cancer.  One of these, sanofi-aventis' cabazitaxel (Jevtana) has already been filed and DDMAC review is expected in the summer, meaning the drug could possibly get approval in the 2nd-line setting after Taxotere by September in an area of high unmet need since there are few options available in this setting.  The data is expected to be presented at ASCO next week, so more on that then.

So now we have two potential therapeutic options before and after Taxotere in 2010 alone, which is progress indeed.

What other compounds are there?

There are a number of agents that I like. Cougar and J&J's abiraterone is probably the most advanced. It is an inhibitor of 17,20 lyase that essentially throttle testesterone production in the testes and adrenal glands.  Millennium-Takeda also have a similar compound in earlier development called TAK700.  The two appear to differ in that one is steroidal and the other is non-steroidal, but whether this will make any meaningful difference isn't yet clear.  Time will tell.  

The abiraterone trials are not scheduled to complete until mid 2011 at the earliest, so assuming the data is positive, approval likely won't happen until the 2nd half of 2012, giving Dendreon a two year commercial advantage over the competition, who are mostly testing their compounds in the post Taxotere setting, at least initially.

Perhaps the most exciting agent from a biology perspective is MDV3100 from Medivation/Astellas, which I have written extensively about in past blog posts.  Essentially, the current androgen blockers are fairly ineffective at controlling aggressive disease so a more complete inhibitor of the Androgen Receptor (AR) may offer a better chance of making an impact.  Medivation have quickly realised that their real opportunity may well be either after hormonal therapies, in combination with them, or perhaps even in place of them earlier in the disease and have announced several new phase II and III trials will commence later this year.  Astellas have significant advantage over J&J as a partner since they already have a strong urology franchise, which is vitally important going forward.

Several other therapies interest me too, but they will be the subject of another blog post later during this meeting as the mutations and critically expressed pathways as the disease progresses may well drive future therapeutic interventions.

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Gefitinib first-line treatment of locally advanced or metastatic non-small cell lung cancer

By on May 27, 2010

After the news yesterday about Bayer's sorafenib being rejected by NICE in liver cancer comes another oncology decision, this time a positive one, and good news for AstraZeneca and gefitinib (Iressa).

The new guidance states:

"Gefitinib is recommended as an option for the first-line treatment of people with locally advanced or metastatic non-small-cell lung cancer (NSCLC) if: 

• they test positive for the epidermal growth factor receptor tyrosine kinase (EGFR-TK) mutation and 

• the manufacturer provides gefitinib at the fixed price agreed under the patient access scheme."

Iressa has had a somewhat chequered history over the last few years, first with the fast track approval in the US on promising phase II data and then the down side of phase III trials failing to show any clear improvement in outcome while OSI/Roche's erlotinib (Tarceva) demonstrating a small but significant survival benefit.

It looks like Iressa is coming back from the dead after all, at least in Europe.

According to FiercePharma, a deal was successfully struck with the agency:

"The lung cancer pill got a recommendation from the cost-effectiveness watchdog for use by the National Health Service, but only after the company offered an unusual fixed-price arrangement. Iressa will be supplied to the NHS at £12,200 ($17,560) per patient, regardless of how long treatment lasts. And the NHS won't pay at all for patients who use Iressa for less than three months."

So in the UK, sorafenib would cost around £27K, whereas gefitinib would cost £13K, both offering a couple of months increased survival in liver and lung cancer, respectively.  The difference in the two situations is that patients can be now screened for the EGFR mutation in lung cancer (which wasn't known at the time of the original approval), thereby preselecting which patients are most likely to respond. There is no biomarker associated with VEGF therapy yet, as far as I'm aware.

As to what will happen in the US, we'll have to wait and see.

Modified measles virus shows potential for treating childhood brain tumors

By on May 26, 2010

Whew, that headline caught my attention just now on the Nationwide Children’s Hospital site while searching for information on medulloblastoma, a form of brain cancer that tends to affect children.

After all the recent brouhaha in the UK over Andrew Wakefield being struck off for professional misconduct relating to his role in the MMR vaccination scandal, tensions may be raised at the idea of using a modified form of the measles virus to treat a childhood brain cancer.

According to the hospital’s press release:

Vaccine strains of measles virus have been used to kill tumor cells in a number of tumor types including one type of adult brain tumor. One vaccine strain of measles, the Edmonston strain, targets the cell surface receptor CD46 to gain entry into susceptible cells. “This preference most likely explains the efficacy of Edmonston strains in killing tumor cells, given the high level of expression of CD46 in multiple tumor types,” said Dr. Raffel. “It is also the reason we chose to explore a modified Edmonston’s strain of measles virus for use in medulloblastoma.”

You learn something new every day.

This news comes hot on the heels of some other research conducted in pediatric brain tumors at St Jude Hospital in Memphis, which reported that:


“Twelve percent of tumors in this study had extra copies of the gene PDGFRA. Researchers reported similar gene-expression patterns associated with high levels of PDGFRA were also found in childhood tumors without extra copies of the gene. Extra copies of PDGFRA were even more common in tumors from children who had received brain irradiation for treatment of earlier cancers.”

As someone who experienced a malignant childhood cancer myself, it’s always gratifying to see research ongoing in this area and improvement in 5-year survival rates.

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Bayer’s Nexavar fails to gain NICE approval in liver cancer

By on May 26, 2010

"The drug, also known as sorafenib, extended lives by an average of 2.8 months at a cost of 27,000 pounds ($38,853) for each patient, NICE said. The Leverkusen, Germany-based company had offered to pay for every fourth pack of Nexavar when used to treat hepatocellular carcinoma, a type of cancer that starts in the liver. Few patients with the disease are able to undergo the surgery that could potentially cure them, NICE said." 

Source: Bloomberg

No surprises there really and consistent with the approach the National Institute for Clinical Excellence (NICE) has taken over the last few years.  You can read what the agency had to say on the matter here. Basically, Bayer offered NICE a deal whereby every 4th pack of sorafenib (Nexavar) would be free, but that wasn't enough to sway the decision:

"Sorafenib does not provide enough benefit to patients to justify its high cost."

It's interesting that my US colleagues always point to this kind of decision as evidence of rationing but it's really an access issue based on who holds the budget strings.  

In the US, drugs might get approved at whatever cost the manufacturer chooses for now, but insurance companies and the CMS may put all sorts of strings attached such as certain conditions, formulary tiers, pre-authorisation etc and in the end the patient also has a choice whether they can and want to afford the co-pays that go with those decisions.  They may after all, still say no, that the price asked is too high a price to pay based on their means.  A drug in a tier 3 or 4 category will have a very different co-pay from a tier 2 drug, for example.

Still, in the end, who pays the Ferryman is still the moot point and sometimes Pharma forget that the days of charging exhorbitant prices that neither the healthcare systems nor the people can afford will one day come to end with excessive price charging.  

Ultimately, it's an unsustainable business model that gives Pharma a bad name synonymous with oil and tobacco companies. Perception is reality sometimes. Eventually the actions of a few will affect the sensibleness of most and in the US we will all get to deal with more systematic price controls and constraints based on the likes of health economics, comparative effectiveness and cost utilities etc whether we like it or not.

Outside of oncology, very few companies consistently engage in head to head comparative trials to prove their drug is more effective or cost effective than the standard of care.  This will ultimately change over time as the authorities get tougher.

In the long, the cost of doing business ie conducting clinical trials, will go up and the burden of proof will shift dramatically.

End of life care and treatment raises all sorts of poignant yet important questions.  Do we need a greater focus on wellness rather than palliation? What about research into better models and biomarkers so that earlier detection of cancer, where intervention can have most effect, can be initiated? Should the needs of the few (eg in the end of life situation) outweigh the needs of the many? Given the limited resources available, how best should they be allocated and invested?  

If you look at the Nexavar situation on reflection, how would that $38K be best spent for the greatest benefit given that there isn't a bottomless pit of money?

These are always tough decisions for anyone to make, especially when a relative or loved one may be involved.  Rather than the PR and media hysteria that inevitably follows these sort of rejections, hard and tough though they may be, it would be nice to see a broader public debate around some of the wider strategic healthcare issues facing us all.

Are we becoming immune to daily gene announcements?

By on May 11, 2010

The other day I clicked on a link someone shared on Twitter about new findings in breast cancer genes, which sounded really cool and interesting.  On clicking through it turned out to be a rather disappointing Reuters release on several fronts:

  1. Where's the link to the original article (in these days of social sharing leaving it out is plain lazy)?
  2. What/where are the "five common genetic factors" exactly?  No mention is made of them.
  3. What does this finding actually mean?
  4. What's the 'wow' factor here rather than the 'so what' factor?

I don't know about anyone else, but daily press releases and assaults in the media about identification of yet more gene blah blah that may or may not be relevant becomes anaesthetising after a while.

After a while, I finally tracked down the actual article in Nature Genetics myself to see what the data actually said (reference below with link to the paper for those interested).

What the researchers did was interesting; they conducted a large genome-wide study (GWAS) in around 8,000 people, approx. half of whom had a family history of breast cancer and half did not (controls). They then studied the DNA of another 24,000 women, with and without breast cancer.  By analysing over half a million SNP's, they were able to identify new 5 loci on chromosomes 9, 10 and 11 which if present, represent an increased risk of developing breast cancer.  This is in addition to 13 gene variations already identified in previous research.

Many of you will be aware of two high risk genes which are more likely to be defective in someone with breast cancer, known as BRCA1 and BRCA2.  These genes often confer higher risk of breast or ovarian cancers and can be tracked in families to try and pick up the cancer earlier. More recently, they have become targets for therapeutic intervention with PARP inhibitors such as AstraZeneca's olaparib in BRCA-positive breast and ovarian cancers.  More on this in another post. 

But what if these 5 new gene variations are also important and early identifiers of increased risk?

The reason that these findings are important is that as Prof Bert Vogelstein of Johns Hopkins never tires of pointing out at AACR meetings, most cancers, including breast cancer, are often diagnosed relatively late in their development and people die from the last 3 years of metastatic disease because the cancer went undetected for 20 odd years. 

GWAS as a field is also becoming more relevant, highlighting distinct subsets of
patients who can then be evaluated for prognosis, biomarkers, efficacy
and tolerability differences.

We still have very few methods of efficient and effective early detection, but what GWAS may allow us to do in future when we have more complete information (and gene testing is cheap, reliable and more widely available) is to potentially run screens to identify those most at risk for cancer.  These people could then be monitored more closely and watched diligently for early signs of cancer appearing.  Early stage cancer is potentially curable with surgery.  Inevitably, preventative studies could also be considered for high risk groups in future.

So these findings will have little immediate impact now, but in future if replicated, they could form the backbone of a comprehensive strategy to identify those people most at risk from developing cancer.  If we think about it, the enormous cost of end of life medical care massively dwarfs what the cost of earlier intervention and potential cure via surgery with or without neoadjuvant therapy would be.  Ultimately, we need this kind of data to move to a wellness model rather than a palliative model.

I would like to acknowledge my buddy Scott Hensley at NPR Health for prodding me into explaining the rationale behind my grump on Twitter about the flood of 'so what' rather than 'oh wow' gene data that constantly abounds daily.  If you're not following him on Twitter or listening to his awesome NPR Health podcasts on iTunes or the web, you should consider it!

ResearchBlogging.org
Turnbull, C., Ahmed, S., Morrison, J., Pernet, D., Renwick, A., Maranian, M., Seal, S., Ghoussaini, M., Hines, S., Healey, C., Hughes, D., Warren-Perry, M., Tapper, W., Eccles, D., Evans, D., Hooning, M., Schutte, M., van den Ouweland, A., Houlston, R., Ross, G., Langford, C., Pharoah, P., Stratton, M., Dunning, A., Rahman, N., & Easton, D. (2010). Genome-wide association study identifies five new breast cancer susceptibility loci Nature Genetics DOI: 10.1038/ng.586

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The lull before the Dendreon storm?

By on April 29, 2010

Today's post is going to be relatively short as I'm knee deep (literally) reviewing poster handouts from the recent AACR meeting, but while reading translational medicine data I came across a poster on sipuleucel-T basically explaining that it engages the immune system and activates or stimulates priming of T-cells in asymptomatic disease.  

Like many out there I'm quietly wondering what will happen tomorrow with Dendreon's PDUFA date due on Saturday May 1st.  We can reasonably assume a response on sipuleucel-T (Provenge) might be forthcoming on either Friday or Monday.

Given the gap in available treatments between castration resistance (CRPC) and stage IV metastatic disease, I'm hoping Provenge receives approval on the basis of the four month survival advantage after a somewhat rocky path along the journey.  Approval could well kick off what may well turn out to be a new era, with other therapies also in late stage development, namely OrthoBiotech/Cougar's abiraterone and Medivation/Astellas' MDV3100, which are both seeking to test their efficacy and safety and in phase III trials for CRPC.

Non-approval could well be a disaster for a company who has invested so much into immunotherapy as their lead product, investors will likely be very unhappy and Monday could turn into a blood bath.  I'm more inclined to be positive though, and my educated guess is that approval will be forthcoming given Dendreon met the pre-defined FDA targets.

We shall see.

{UPDATE: The FDA officially approved Dendreon's Provenge today 29-4-10, see comments below for FDA links and materials including the PI.}

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New developments in castration resistant prostate cancer – MDV3100

By 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:

Picture 6

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!


ResearchBlogging.org
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

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

By 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.

ResearchBlogging.org
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 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

ResearchBlogging.org
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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