In 2004, the FDA approved Alimta for the treatment of mesothelioma. Before
that, there was no drug that had been approved specifically for meso,
and most patients were steered to multi-modal therapy protocols that included
radical surgery. Oncologists and Eli Lilly touted Alimta/Cisplatin as
the new "standard of care." A large randomized trial showed
that the Alimta/Cisplatin regimen offered about 12.1 months of life rather
than Cisplatin alone, which offered about nine. Since then, many surgeons
have commented that they are seeing fewer patients, as primary care doctors
have begun to bypass surgeons and refer their patients directly to the
town oncologist.
Experts in the field continue to differ, and most, like thoracic surgeon
Dr. Raja Flores, agree that "controversy still exists with regard
to standard care."
[1] The reason that experts disagree is that promising results and longer
lives seem to result from multi-modal therapy, which uses chemotherapy
in conjunction with some form of surgery. Chart D, "Cocktails and
single shots: measuring drugs by the numbers," provides an overview
of available drugs and median survival times. Critics note that the University
of Chicago Alimta/Cisplatin study that led to FDA approval barely reached
levels of statistical significance,
[2] prompting some to conclude that if Alimta/Cisplatin is the standard of
care, it's not by much.
Clinical trials: more drug cocktails
Bewildering, experimental, little accountability, less data, and fraught
with complex rules for eligibility, clinical trials are sometimes the
only hope a mesothelioma patient has. Most involve combinations of drugs.
By definition, as "experimental," there is little if any data
about survival times or recurrence rates. On the other hand, cost is rarely
a factor, as the sponsor of the trial normally supplies the drugs and
the attendant medical care.
A full listing and description is available in Chart E, "Best web
resources for clinical trials." There are about nine trials in the
U.S. still recruiting patients. The client and his doctor should look
at each one carefully.
Cocktails and single shots: measuring drugs by the numbers
Cytotoxic agent |
Median survival |
Methotrexate-alpha interferon-gamma interferon |
17
[1]
|
Interleukin-2 |
15.8
[2]
|
Cisplatin-epirubicin |
13.3
[3]
|
Cisplatin-pemetrexed (Alimta) |
12.1
[4]
|
Cisplatin-raltitrexed |
11.2
[5]
|
Ranpirnase |
11
[6]
|
Methotrexate |
11
[7]
|
Vinflunine |
10.8
[8]
|
Vinorelbine |
10.6
[9]
|
Doxorubicin |
7.3
[10]
|
Gemcitabine |
9.5
[11]
|
Cisplatin |
9.3
[14]
|
Oxaliplatin-raltitrexed |
9.3
[12]
|
No surgery or chemotherapy |
7
[13]
|
We were able to find treatment costs for Alimta/Cisplatin only, which is
as follows: Every course consists of 6 cycles. A patient may receive up
to three courses, for a total of 18 cycles. The estimated cost for one
course is between $60,000 and $80,000.
Chart Footnotes |
1 |
Halme et al, Br J Cancer. 1999 Aug;80(11):1781-5. Study included 26 patients. |
2 |
Castegneto B et al, Lung Cancer. 2001 Feb-Mar;31(2-3):303-10 |
3 |
Berghmans et al, Lung Cancer. 2005 Oct;50(1):75-82. 69 patients in this study. |
4 |
Vogelzang et al, J Clin Oncol. 2003 Jul 15;21(14):2636-44. The only FDA-approved
treatment for malignant pleural mesothelioma is a chemotherapeutic doublet
of cisplatin and pemetrexed (Alimta). Addition of folic acid and vitamin
B12 in the Vogelzang study cited here significantly reduced toxicity without
adversely affecting survival time. In the study, 2/3 of patients were
epithelial type, and 78% were stage III or stage IV. Only patients ineligible
for surgery were used. Results were not based on a full intention-to-treat
analysis, and were reported as being only fractionally inside the range
of statistical significance. |
5 |
van Meerbeeck et al, Proceedings of the American Society of Clinical Oncology,
2004. Abstract 7021. |
6 |
Vogelzang et al, Program and abstracts of the American Society of Clinical
Oncology 36th Annual Meeting; May 20-23, 2000; New Orleans, Louisiana.
Abstract 2274. Pemetrexed is approved for use in the United Kingdom by
the National Institute for Health and Clinical Excellence, Reuters, July
9, 2007. Pemetrexed with cisplatin is the standard of care for mesothelioma
in Australia, www.ohsrep.org.au. |
7 |
Solheim et al, Br J Cancer. 1992 Jun;65(6):956-60. Study included 60 patients. |
8 |
Talbot et al, J Clin Oncol. 2007 Oct 20;25(30):4751-6. |
9 |
Steele et al, J Clin Oncol. 2000 Dec 1;18(23):3912-7. Study included 29 patients. |
10 |
Lerner et al, Cancer. 1983 Dec 1;52(11):1981-5. |
11 |
Byrne et al, J Clin Oncol. 1999 Jan;17(1):25-30. |
12 |
Fizazi et al, J Clin Oncol. 2003 Jan 15;21(2):349-54. |
13 |
Herndon et al, Chest. 1998 Mar;113(3):723-31. |
[1] Flores and Zakowski, Id.
[2] Steele and Klabatsa, Chemotherapy options and new advances in malignant
mesothelioma, Annals of Oncology, Jan. 2005