Does adjuvant systemic therapy with interferon-alpha for stage II-III melanoma prolong survival?

The experience with interferon-alpha in malignant melanoma resembles, to some degree, the experience with various kinds of adjuvant immunotherapeutic agents where 25 years of phase III trials of adjuvant therapy in stage II-IIII melanoma have not defined a standard therapy. Most trials failed to demonstrate an impact on disease-free survival and overall survival. Currently, data from 12 randomized interferon-alpha trials are available. The data in almost 3000 patients, approximately 50% of the total patient population, is immature and thus, inconclusive. Mature trials show that interferon-alpha significantly prolongs disease-free survival, but does not prolong overall survival, across different dose levels. Ultra-low-dose (1 MIU flat dose), interferon-alpha failed to even have an effect on disease-free survival. Although two trials with high-dose (10-20 MIU/m(2)) interferon-alpha have shown an impact on overall survival, these data are inconclusive since this impact was transient, inconsistent in subsequent trials, and the data was somewhat immature. Inconsistent results have also been observed for intermediate- (5-10 MIU flat dose) and low-dose (3 MIU flat dose) interferon-alpha regimens. The results, overall, suggest that these doses do have an impact on disease-free survival, but not on overall survival. Preliminary results regarding distant metastasis-free survival (the closest surrogate for overall survival available) of the very large European Organisation for Research and Treatment of Cancer (EORTC) 18952 trial suggests that there is a benefit with long-term low intermediate doses and support the anti-angiogenic concept of long-term maintenance treatment with interferon-alpha. The efficacy of short-term high-dose and long-term intermediate-dose treatment is being investigated in new trials. For now the role of interferon-alpha still remains to be determined and its use should be restricted to the setting of clinical trials.     

Which patient is a candidate for treatment with efalizumab and why?

With the coming of the biological therapies, long-term maintained control of psoriasis is becoming a reality and means a significant improvement in the quality of life in some patients with persistent clearing of the disease. This result was difficult to obtain previously. Efalizumab, a recombinant IgG1 anti-CD11a antibody approved for the treatment of psoriasis in moderate-to-severe chronic plaques, has an excellent safety profile and its therapeutic results in the clinical practice have surpassed the expectations based on the clinical trials. At 12 weeks of treatment (when its efficacy should be evaluated), a PASI 75 response can be expected in 35 to 40% of the patients and a PASI 50 response in two thirds of them. This degree of improvement may be maintained and may even increase in 80% of the patients, making it possible to achieve an almost complete clearing in more than 40% of the patients who continue the treatment over several years. Localized, transitory exacerbations may appear, especially in the beginning of the treatment, but these can generally be managed in combination with another treatment. There may also be generalized inflammatory outbreaks, especially in patients with scarce or null response, who require treatment with a rapid effect systemic drug at the onset. This is because they may be a prelude to the development of rebounds, that may acquire an erythrodermic or pustular morphology or be accompanied by arthritis, and which tend to appear after the sudden withdrawal of the drug. An adequate selection of the patients may maximize the possibilities of success. Patients without arthritis and with stable, extensive and non-inflammatory forms of the disease tend to be the best candidates. Special attention should be given to the administration of systemic agents in transition regimes when efalizumab is introduced or withdrawn. The clinical criteria is fundamental to optimize the therapeutic results with efalizumab, that may be an attractive challenge but may also be an especially satisfactory therapeutic option when long-term control is the disease is proposed.     

Quality of life in melanoma patients during adjuvant treatment with pegylated interferon-α2b: patients' and doctors' views

Treatment of malignant melanoma with IFN-α has been associated with significant side-effects. The aim of this retrospective monocentric non-randomized study was first to evaluate the impact on quality of life (QOL) in 30 melanoma patients treated with once weekly 2?μg/kg PEG-IFN-α2b for 18 months, and second to examine whether there is a difference in patients' and physicians' perception of QOL. Data on QOL were collected by means of the EORTC QLQ-C30 questionnaire completed by the patient before consultation at baseline and every three months during treatment. A second questionnaire was filled out independently by the physician, based on the consultation and patient file. All data were routinely collected in an outpatient care unit. At baseline, patients had more favorable mean values on almost all dimensions of the EORTC QLQ-C30 than follow-up assessments. In comparison to published low-dose IFN-α2a data, once weekly 2?μg/kg PEG-IFN-α2b was associated with stronger impairment in most QOL single dimensions but with almost no differences regarding the global health status. QOL documented by physicians was significantly higher than QOL from the patients' questionnaires in all QOL dimensions (p<0.05). PEG-IFN-α2b has measurable effects on QOL. Measuring QOL based only on physicians' patient files without explicitly determining patients' assessments leads to a profound underestimation of impairment of QOL.     

Is the survival rate for acral melanoma actually worse than other cutaneous melanomas?

It is still not clear whether the survival rate for acral melanoma (AM) is better or worse than that of cutaneous melanoma developed at other sites. We sought to evaluate the difference in survival depending on the primary tumor site of cutaneous melanoma. We retrospectively reviewed primary cutaneous melanoma cases diagnosed at Samsung Medical Center, a tertiary institution in Korea, from January 1995 to July 2017. The cohort consisted of 642 patients, with 389 non-acral cutaneous melanoma (NACM) patients and 253 AM patients. The AM patients had a higher percentage of stage 0 diagnoses than the NACM patients (31.6% vs 6.9%, respectively). The factors associated with overall survival were primary tumor site, sex, age, American Joint Committee on Cancer stage, surgery and medical treatment (P < 0.05). Non-acral sites showed worse survival in multivariable analysis (hazard ratio [HR], 1.457; 95% confidence interval [CI], 1.051–2.020; P = 0.0240). Among the NACM, melanomas on the trunk were associated with a higher risk of mortality compared with AM (HR, 1.883; 95% CI, 1.142–3.107; P = 0.0131). Acral melanoma was associated with a better prognosis than non-acral melanoma, specifically when located on the trunk, in Korean patients.