metastatic melanoma have a low survival rate.
Studies indicate that an ipilimumab which is a novel monoclonal
antibody when combined with an anticancer drug dacarbazine may provide benefit
in patients with metastatic melanoma
. These studies were conducted in small
groups of patients.
a new monoclonal antibody approved by the FDA in March 2011 for the treatment
of metastatic melanoma
. It is marketed as Yervoy in the United States. The results of a Phase
III study that the drug underwent have been recently published in the New
England Journal of Medicine. The study was sponsored by the pharmaceutical
giant, Bristol-Myers Squibb and was conducted between August 2006 and January
2008. It compared the effects of ipilimumab or placebo when combined with
dacarbazine on survival in 502 patients with previously untreated metastatic
melanoma and a life expectancy of 16 weeks or more.
Patients were administered ipilimumab (at a dose of
10 mg/kg) plus dacarbazine or dacarbazine plus placebo at weeks 1, 4, 7, and
10, followed by dacarbazine alone every 3 weeks through week 22. Neither the patients nor the treating
doctors were aware as to which medications the patients received. This was done
to avoid any bias in the results. At week 24, patients without any adverse
effects during this period were put on either placebo or ipilimumab every 12
weeks until the disease progressed further, the patient developed side effects,
or the study ended. The tumor was assessed radiologically as well as by
comparing photographs at specific times during the study.
Some patients discontinued the treatment due to
disease progression (more in the dacarbazine plus placebo group) or the
development of adverse effects (more in the ipilimumab plus dacarbazine group).
results found that overall survival was better in the ipilimumab-dacarbazine
group. This group however also showed a higher incidence of adverse effects
like increase in liver enzymes, diarrhea, itching and rash.
Compared to previous studies, the research found a
decrease or absence of certain adverse effects in this study such as digestive
tract perforations, hypophysitis (inflammation of the pituitary gland),
diarrhea and colitis. However, increase in liver enzymes was higher when
compared with previous studies. One reason could be that dacarbazine, which is
known to cause liver damage, was also administered to the patients.
The study thus
concluded that a combination of ipilimumab with dacarbazine improves survival
when compared to dacarbazine and placebo in patients with previously untreated
1. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C et al.
Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma. N
Engl J Med 2011; 364:2517-2526.