Glioblastoma, Avastin, and cost of cancer drugs

Cancer Drugs Bring Cost-of-Life Decisions
Following is a(n impossibly long) link to an article that appeared in the September 27 edition of The Oregonian by AP writer Marilynn Marchione, "Cancer drugs bring cost-of-life decisions." Some excerpts: "For the past decade, new cancer-fighting drugs have topped $5,000 a month. Only a few of these keep cancer in remission so long that they are, in effect, cures. For most people, the drugs may buy a few months or years. Insurers usually pay if Medicare pays.... Medicare usually pays if the federal Food and Drug Administration (FDA) has approved the use.... When is a drug considered cost-effective? The most widely quoted figure is $50,000 for a year of life.... Higher costs seem to be more accepted for cancer treatment than for other illnesses, but there's no rule on how much is too much."

http://news.yahoo.com/s/ap/20100927/ap_on_he_me/us_med_costly_cancer_drugs;_ylt=Avsk6pTag662ngRCGc3GgBas0NUE;_ylu=X3oDMTN2bDM3N2hvBGFzc2V0A2FwLzIwMTAwOTI3L3VzX21lZF9jb3N0bHlfY2FuY2VyX2RydWdzBGNjb2RlA21vc3Rwb3B1bGFyBGNwb3MDMTAEcG9zAzcEcHQDaG9tZV9jb2tlBHNlYwN5bl9oZWFkbGluZV9saXN0BHNsawM5MzAwMGNhbmNlcmQ-

Avastin for Metastatic Breast Cancer
The October 4 issue of Newsweek (p. 50) has an interesting article about Avastin and its use specifically in metastatic breast cancer (Begley S. It's not about rationing: why the FDA may reverse course on Avastin.) In the U.S., Avastin (bevacizumab) is approved for treatment of metastatic colorectal cancer, non-squamous non-small cell lung cancer, metastatic breast cancer (MBC), glioblastoma (that's me), and metastatic renal cell carcinoma. In 2008 FDA gave "fast track" approval for Avastin in MBC, conditional on the manufacturer (Genentech) running additional clinical trials of the drug's safety and efficacy. Turns out that not only did Avastin not keep women with MBC alive, but it seems as if the drug's toxicity cancels out any benefit. These dismal results are what led an FDA panel to vote 12-1 in July to rescind the conditional approval of Avastin for MBC. A decision by the FDA is expected by year's end. Of course there are stories galore of women with MBC who claim to be alive because of Avastin. There are always patients who live longer than average; they attribute it to the treatment. That some women did live longer on Avastin may simply reflect the natural heterogeneity of the disease and say nothing about the therapy.

Avastin for Glioblastoma (Moen MD. Bevacizumab: in previously treated glioblastoma. Drugs 2010;70:181-9)
Glioblastomas are malignant primary brain tumors. They are the most common type of gliomas, and account for 18.5% of all primary brain and CNS tumors. Standard treatments for glioblastoma include surgical removal of as much of the tumor as possible (check), postoperative radiotherapy (check), and chemotherapy with temozolomide (check). The prognosis for patients with glioblastoma is poor, with an estimated 5-year survival rate of 3.4%. Glioblastomas are particularly aggressive, and are associated with rapid growth and angiogenesis (blood vessel growth); the formation of new blood vessels is essential for tumor development.

I started bevacizumab (Avastin) yesterday. Bevacizumab is a recombinant humanized monoclonal antibody that binds to human vascular endothelial growth factor (VEGF) and inhibits angiogenesis and hence tumor growth. Bevacizumab was approved by the FDA in May 2009 as a single agent for the treatment of glioblastoma with progressive disease following prior therapy. It is administered as an intravenous (IV) infusion over 30 minutes. The recommended dose for treatment of glioblastoma is 10 mg/kg every 2 weeks. Patients should continue treatment until disease progression or unacceptable toxicity. Given the nature of the disease, bevacizumab was generally well tolerated in clinical trials.

A word about cost and effectiveness of Avastin for glioblastoma: At my dose, the cost of a single infusion is north of $4500, or about $118,000 a year, though few patients live that long. The effectiveness of Avastin in glioblastoma is based on an improvement in objective response rate. There are no data demonstrating an improvement in disease-related symptoms or increased survival with Avastin. Yet treatment with temozolomide and bevacizumab are the standard of care today for treatment of glioblastoma. I failed the former and am on the latter.

My intent is not to paint an overly morbid or pessimistic picture about my situation. I feel pretty good, and I have a lot to be thankful for. But on the other hand, I do need to be realistic (while cautiously optimistic) about where we stand. Count my blessings, and take one day at a time. By the way, I am now 10 months out from my diagnosis on Thanksgiving 2009.

Trip to coast; weekend in Redmond

A week ago we spent two nights at The Ocean Lodge in Cannon Beach, complements of Andy/Ali/Pete/Tracy for our 40th anniversary (thanks, guys!). One day was an absolutely perfect, warm and sunny late summer day. We ate lunch out a couple of times, enjoyed the spa and the nice complementary continental breakfasts. With free DVD rentals, we watched two movies each night. Came home to catch up on the mail and laundry, then headed off to Redmond on Friday for a visit with Andy, Ali, Brady, and Drew. We babysat the boys on Friday night so that A&A could go out to dinner on their 6th anniversary. The boys are growing up so fast, and we really had a good time with them. We came back on Sunday afternoon, taking therapy dog Larue along for another visit. Larue seems happy to be back on my lap. Today was one of those warm (85 degrees), sunny days, with the leaves turning color. Shows Portland and Oregon to be a special, special place, particularly on a day like this at this time of the year.

Brain cancer awareness

We hear lots about the epidemics of breast cancer in women (Susan G. Komen Breast Cancer Foundation, etc.) and prostate cancer in men (Michael Milken's Prostate Cancer Foundation, etc.), as well we should. We've had several friends with one or the other diagnosis, some of whom have not survived.

Several types of cancer fly under the radar, including breast cancer in men and brain cancers in general. The following is from a recent review in The New England Journal of Medicine [Wen PY, Kesari S. Malignant gliomas in adults. N Engl J Med 2008;359:492-507].

Malignant gliomas account for approximately 70% of the 22,500 new cases of malignant primary brain tumors that are diagnosed in adults in the U.S. each year. The annual incidence of malignant gliomas is approximately 5 cases per 100,000 people. Each year, more than 14,000 new cases are diagnosed in the U.S. The incidence of these tumors has increased slightly over the past two decades, especially in the elderly, primarily as a result of improved diagnostic imaging. Malignant gliomas are 40% more common in men than in women and twice as common in whites as in blacks. No underlying cause has been identified for the majority of malignant gliomas.

Malignant primary brain tumors
Malignant gliomas
Glioblastomas

Glioblastomas account for approximately 60 to 70% of malignant gliomas. The median age of patients at the time of diagnosis is 64 years in the case of glioblastomas. Although relatively uncommon, malignant gliomas are associated with disproportionately high morbidity and mortality. Despite optimal treatment, the median survival is only 12 to 15 months for patients with glioblastomas.

An abbreviated list of 25 famous brain tumor patients who died as a result of their disease (Wikipedia)
Sam Bottoms, actor (The Last Picture Show)
Susan Hayward, Academy Award-winning actress
Irene Ryan, Granny from The Beverly Hillbillies
Jack Brickhouse, sports broadcaster
Gene Siskel, film critic and TV partner of Roger Ebert
Johnnie Cochran, defense attorney for O.J. Simpson
George Gershwin, jazz and classical music composer
Bill Haley, leader of one of the first rock-and-roll bands, The Comets
George Harrison, Beatle
Bob Marley, reggae king
Ethel Merman, Broadway singer and actress
Lou Rawls, soul/jazz/blues singer
Lee Atwater, chairman of the RNC
William J. Casey, director of the CIA
Edward (Ted) Kennedy, U.S. senator
Robert Novak, political pundit
Thor Heyerdahl, marine biologist on Kon-Tiki expedition
Eero Saarinen, architect whose work included the Gateway Arch in StL
Raymond Carver, writer and poet
Mary Shelley, author of Frankenstein
Dick Howser, MLB shortstop and manager
Tug McGraw, MLB pitcher and father of CW singer Tim McGraw
Bobby Mercer, MLB player and broadcaster
Dan Quisenberry, MLB pitcher
Wilma Rudolph, Olympic gold medalist in track

Busy week in review

I had another MRI on Tuesday of this week, then had an appointment with my oncologist on Thursday and my radiation oncologist on Friday. Long story short: "...Apparent progression of disease within the left parietal lobe...." Disappointing news, but not totally unexpected. I've noticed fairly dramatic worsening of my gait abnormalities in the past couple of weeks, probably brought on by brain swelling as a result of tumor growth. So now I'm back on the corticosteroid dexamethasone to hopefully reduce the swelling. In addition I will most likely begin an IV chemotherapy drug bevacizumab (Avastin) within the next couple of weeks. Avastin is approved by the FDA for treatment of glioblastoma as a single agent for patients with progressive disease following prior therapy. It is administered by intravenous infusion every two weeks. Treatment is usually continued until disease progression or unacceptable toxicity. Given the nature of the disease, Avastin was generally well tolerated in two small clinical trials. My prior therapy was radiation therapy and the oral agent temozolomide (Temodar). I am hopeful that I will get some benefit from the Avastin. As Marge says, we have to play with the cards we're dealt.

We also went to Ed Caldwell's funeral on Wednesday. Ed was a wonderful and gentle man who became the first African-American graduate of the Oregon State University College of Pharmacy. He finished his pharmacy career at Providence St. Vincent Medical Center's outpatient pharmacy. I got to know Ed when I was an inpatient pharmacist there at the same time. Coincidentally I worked with Ed's wife Donna at Kaiser Permanente for several years after I left PSVMC and before Donna retired. Great people, and a wonderful couple. Ed will be missed by his many friends. If you look up the word "gentleman" in the dictionary, you will find a picture of Ed Caldwell.

Pete and Tracy and their girls are visting with Andy and Ali and their boys this weekend. The circus is on their agenda for tomorrow. I can imagine it would be a circus without the circus with the four little kids. Lucy happened to be running by when I was on the phone with Pete after they arrived in Redmond this evening. Pete asked her if she wanted to say hello to Grammy and Papa. She replied very politely, "No thank you." (Too busy to talk.)

My old Kaiser work group is having an end-of-summer get-together on Sunday. We are looking forward to seeing the old gang. And finally, we are getting together with Jim and Susan Sanger, who now live in St. Louis. I worked for Jim at Good Samaritan Hospital before I went to PSVMC. Small pharmacy world in Portland.

P.S. We have a new email address: nomarmuilenburg@frontier.com

Are you ready for some football?

College football gets started tomorrow, Thursday, September 2. No. 14-ranked USC, unable to find an opponent on the mainland, will travel to Hawaii to play the Warriors. Prior to the year 2000, the University of Hawaii's men's teams were all referred to as the Rainbow Warriors, complemented by an athletics logo featuring a rainbow. However, in a controversial marketing strategy over which many at the University and throughout Hawaii have misgivings, the school changed its athletics logo to a stylized "H" and allowed each team to pick its own team name. This has led to the current situation, where the basketball, swimming and diving, and tennis teams have retained the team name of "Rainbow Warriors"; the baseball team adopted the name "Rainbows"; and the football, golf, and volleyball teams have adopted the name "Warriors". But I digress....

Also on Thursday the unranked Golden Gophers of Minnesota travel to play the Blue Raiders of powerhouse Middle Tennessee State University of the Sun Belt Conference. (The Blue Raiders of MTSU, located in Murfreesboro, TN, are not to be confused with the Blue Smurfs of Boise State.) Minnesota is picked to be the 11th (last) team in the Big Ten Conference. This is possible only because the conference kept the name "Big Ten" when Penn State was added a few years ago to make an 11-team conference. On Saturday No. 24 Oregon State takes on No. 6 TCU in Dallas, No. 11 Oregon plays unranked New Mexico, Washington plays at BYU, and Washington State plays at Oklahoma State.

Which brings us back to poor ol' USC. A USC football player was bragging to a group of coeds that he finished a jigsaw puzzle in only three months. One girl said, "Three months? You're proud of that?" The Trojan replied, "Yep; on the box it said 4-6 years." [Shamelessly lifted from "The Edge" column in The Oregonian.]

As a public service to the 2 or 3 individuals reading this who may be interested, I've tried to sort out the college athletic conference realignment, which was no easy task. The eleven-member Big Ten conference will add Nebraska to become the Bigger Ten or the New Big Twelve Conference. The Big 12 Conference will lose Nebraska to the Big 10 and Colorado to the Pac-10 to become the New Big 10 or the Little Big 12. The Pac-10 Conference will add Colorado and Utah to become, presumably, the Pac-12. Now here is where it gets interesting; pay attention. The Western Athletic Conference (WAC) will lose Boise State, Fresno State, and Nevada, all of which will join the Mountain West Conference. But the Mountain West will lose Utah to the Pac-10/Pac-12 and will also lose BYU. BYU will play an independent schedule in football but will join the West Coast Conference for basketball and other sports. The West Coast Conference will consist of seven Catholic universities or colleges (Portland, San Francisco, Santa Clara, Gonzaga, Saint Mary's, San Diego, Loyola Marymount), Pepperdine (Church of Christ), and BYU (Mormon). But not for football. So now you know....

End-of-life care

Interesting reading, if you are interested in the topic, that is. A long article about re-thinking end-of-life treatment by Atul Gawande in the August 2 issue of The New Yorker. Gawande is a surgeon at Brigham and Women's Hospital in Boston and an associate professor at Harvard Medical School and the Harvard School of Public Health. He has written several best-selling books. Here is a statistic to ponder: According to Gawande, 25% of all Medicare spending is for the 5% of patients who are in their final year of life, and most of that money goes for care in their last couple of months which is of little apparent benefit.

This article was closely followed by the publication of a study in the August 19 edition of The New England Journal of Medicine. Also included is a related news article and some editorials generated by the study.

1. Gawande A. Letting go. The New Yorker 2010 Aug 2; p. 36-49.
http://www.newyorker.com/reporting/2010/08/02/100802fa_fact_gawande

2. Temel JS, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010;363:733-42.
http://www.nejm.org/doi/pdf/10.1056/NEJMoa1000678

3. Kelley AS, Meier DE. Palliative care: a shifting paradigm [editorial]. N Engl J Med 2010;363:781-2.
http://www.nejm.org/doi/pdf/10.1056/NEJMe1004139

4. McNeil DG Jr. Palliative care extends life, study finds. The New York Times 2010 Aug 18.
http://www.nytimes.com/2010/08/19/health/19care.html?ref=donald_g_jr_mcneil

5. The Oregonian Editorial Board. Rx: a dose of old-fashioned comfort [editorial]. The Oregonian 2010 Aug 19.
http://www.oregonlive.com/opinion/index.ssf/2010/08/rx_a_dose_of_old-fashioned_com.html

Movie review: "Inception"

You may have noticed the lack of recent blogging. Nothing much new about me. I finished my last course of temozolomide (oral chemotherapy) and now await another MRI on September 2, the results of which will hopefully be more definitive than those in the past. Was it pseudoprogression (radiation debris) or is it actual progression? Past MRIs were unable to distinguish between the two. If it was radiation debris, that should now have disappeared.

Since I have no news, I thought I'd compare my review with two published reviews of the movie "Inception," which to date has $261.8 million in ticket sales at movie theaters.

Shawn Levy, The Oregonian: Grade A. A deeply dazzling and immense film about a team of mind-explorers trying to implant an idea in a subject's heavily guarded subconscious. Filled with logical puzzles, jaw-dropping action and audacious visuals, it's the brainchild of Christopher Nolan's "Memento" and one of his special-effects movies. Superb....

“Memento” on the scale of “The Dark Knight”: Dense, operatic, thrilling, puzzling, vexing and utterly, utterly brilliant. A man adept at stealing secrets from people while they dream must reverse his process and plant an idea in someone’s head -- and risk his own sanity in the process. It’s a metaphor for moviemaking, of course, with its dreams-within-dreams-within-dreams (it actually goes much deeper....). But it’s also a mournful and nervy depiction of a man driven by loss and guilt and fear. Leonardo DiCaprio seems still in “Shutter Island” mode, which isn’t a bad thing. But a wonderful supporting cast gives it brightness and lift. And writer-director Christopher Nolan’s visual ideas, pacing and audacity mesmerize.

David Denby, The New Yorker:
Christopher Nolan, the British-born director of “Memento” and of the two most recent Batman movies, appears to believe that if he can do certain things in cinema—especially very complicated things—then he has to do them. But why? To what end? His new movie, “Inception,” is an astonishment, an engineering feat, and, finally, a folly. Nolan has devoted his extraordinary talents not to some weighty, epic theme or terrific comic idea but to a science-fiction thriller that exploits dreams as a vehicle for doubling and redoubling action sequences. He has been contemplating the movie for ten years, and as movie technology changed he must have realized that he could do more and more complex things. He wound up overcooking the idea. Nolan gives us dreams within dreams (people dream that they’re dreaming); he also stages action within different levels of dreaming—deep, deeper, and deepest, with matching physical movements played out at each level—all of it cut together with trombone-heavy music by Hans Zimmer, which pounds us into near-deafness, if not quite submission. Now and then, you may discover that the effort to keep up with the multilevel tumult kills your pleasure in the movie. “Inception” is a stunning-looking film that gets lost in fabulous intricacies, a movie devoted to its own workings and to little else....

Summarizing the movie makes it sound saner than it is. For long stretches, you’re not sure whether you’re in dream or reality, which isn’t nearly as much fun as Nolan must have imagined it to be. Bizarre oddities, which complicate the puzzle but are meaningless in themselves, flash by in an instant. The actors, trying to suggest familiarity with the task of dream invasion, spin off gibberish in the most casual way. Parodies, I assume, will follow on YouTube. And the theologians of pop culture, taking a break from “The Matrix,” will analyze the over-articulate structure of “Inception” for mighty significances....

I would like to plant in Christopher Nolan’s head the thought that he might consider working more simply next time. His way of dodging powerful emotion is beginning to look like a grand-scale version of a puzzle-maker’s obsession with mazes and tropes.

Norm's review:
There are only two (small) things wrong with this movie:
(1) I didn't know what the hell was happening throughout the movie. It might not have helped that I fell asleep for a period of time during the movie, but I put the blame for that on Christopher Nolan.
(2) The movie went on FOR-EVVVV-ERRRR (148 excruciating, painfully slow minutes, to be exact).

So there you go. If you are one of the few who haven't yet seen this movie, you can believe Shawn Levy, or you can believe David Denby. Personally, I side with David Denby. (You can tell I don't get out much.)