Chemotherapy: The Standard of Care?

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

*** POSTED ON FEBRUARY 7, 2008 ***