Skin Cancer & Melanoma

A new type of agent, an oxidative stress inducer, combined with paclitaxel improved survival in patients with metastatic melanoma, compared with paclitaxel alone

GSK and Synta announce STA-4783 collaboration

Integrins have direct effects in stimulating proliferation and preventing apoptosis in cancer cells and mediating proangiogenic interactions between endothelial cells and extracellular matrix. Alterations of expression of various integrins and their receptors have been observed in various cancers in which angiogenesis is known to play a role, including colorectal cancer. Inhibition of specific integrins might thus inhibit both direct effects of integrins on cancer cells and tumor angiogenesis. Inhibitory peptides and anti-integrin monoclonal antibodies are currently being investigated in clinical trials in patients with solid tumors, with early evidence suggesting clinical benefit in disease stabilization with use of an anti-αvβ3 antibody in the settings of colorectal cancer, renal cell carcinoma, and melanoma. Integrin inhibition alone and with other targeted therapeutic approaches should be further investigated in clinical trials in patients with colorectal cancer.

Integrins play an important physiologic role in cell adhesion, and accumulating evidence suggests that they also regulate cell growth, proliferation, migration, and apoptosis. A number of congenital and acquired disease states have been associated with integrins, and small- molecule integrin inhibitors have been approved for treatment of benign hematologic diseases. In cancer, aberrant expression with normal functioning rather than dominant genetic variations of genes coding for integrins has generally been observed. This aberrant expression is mediated through "bidirectional" receptor signaling and interaction with corresponding signals from growth factor signaling pathways, leading to inhibition of apoptosis, induction of cell proliferation, extracellular matrix remodeling, migration, and angiogenesis. From a clinical perspective, a growing number of molecules targeting integrins have been developed for treatment and imaging purposes; clinical studies in melanoma, prostate cancer, and other malignancies are underway. This review summarizes the biology of integrins, the signal transduction pathways they regulate, and their role in different stages of carcinogenesis. Furthermore, it provides a synopsis on the clinical advancements in integrin targeting for therapeutic and imaging purposes in cancer.

When you inspect moles, pay special attention to their sizes, shapes, edges, and color. A handy way to remember these features is to think of the A, B, C, and D of skin cancer-asymmetry, border, color, and diameter.

Since its inception in 1985, the American Academy of Dermatology's National Melanoma/Skin Cancer Screening Program has screened more than 1.7 million people and detected more than 171,200 suspicious lesions. More than 20,000 of these lesions were suspected melanomas—the most serious form of skin cancer.

Genta Incorporated has announced that the company will conduct a new randomized controlled phase III trial of its lead anticancer product Genasense (oblimersen sodium) Injection in patients with advanced melanoma.

Hepatic Arterial Chemoembolization (HACE) May Prolong Survival in Melanoma Patients With Liver Mets

May is National Skin Cancer Awareness MonthWhat Is Your Skin Cancer IQ?Identifying BCC, SCC, and melanoma

At follow-up of more than 2 years, the largest study ever conducted in patients with advanced melanoma has continued to show a trend toward improved survival and a near-doubling of both progression-free survival (PFS) and durable response rates when the targeted antisense drug oblimersen sodium (G3139, Genasense) was added to standard therapy with the alkylating agent dacarbazine (DTIC).

Bayer Pharmaceuticals Corporation and Onyx Pharmaceuticals, Inc. (Emeryville, California) have announced that a phase III trial administering sorafenib (Nexavar) or placebo tablets in combination with carboplatin and paclitaxel in patients with advanced melanoma did not meet its primary endpoint of improving progression-free survival. The treatment effect was comparable in each arm.

Five of seven advanced melanoma patients had significant regression or stabilization of disease after treatment with Ontak (denileukin diftitox, Eisai)

Two of 15 patients with metastatic melanoma had tumor regression after treatment with genetically modified peripheral blood lymphocytes (PBLs)

A Mayo Clinic physician and his colleagues have defined the normal number of melanocytes that are present in Caucasians' sun-exposed skin.

Talabostat (PT-100, Point Therapeutics), an oral, small-molecule inhibitor of dipeptidyl peptidase (DPP) fast-tracked by the FDA for stage IIIB/IV non-small-cell lung cancer, also looks promising in salvage regimens for patients with advanced melanoma or chronic lymphocytic leukemia (CLL

The patient is an otherwise healthy male transferred from an outside hospital with a newly diagnosed melanoma from an unknown primary presenting as a large, left axillary mass.

During the past 18 months, researchers have developed substantial evidence supporting the notion that stem cells play a critical role in the development of at least some cancers, their progression, and the prognosis of patients, including breast, brain, lung, and prostate cancer, multiple myeloma, and melanoma.

On May 6, members of the American Academy of Dermatology (ADA) hope to set a Guinness World Record for the most people screened for skin cancer in a single day.

According to a 2005 survey conducted by the American Academy of Dermatology, 92% of the respondents understood that getting a tan from the sun is dangerous. Yet, 65% said that they think they look better when they have a tan.

ORLANDO-Adding the investigational antisense agent oblimersen sodium (Genasense, G3139) to dacarbazine (DTIC) significantly improved response and survival in patients with advanced malignant melanoma in a phase III trial. John M. Kirkwood, MD, of the University of Pittsburgh Cancer Institute, reported 2-year results at the 41st Annual Meeting of the American Society of Clinical Oncology (abstract 7506) (see Table).

Mohs surgery has been well-established as the gold standard for the treatment of BCCs and SCCs. And, as described in this article, preliminary reports suggest that it may play an equally important role in the management of several other cutaneous malignancies.

Drs. Pennington and Leffellhave provided an excellentoverview of the current uses ofMohs micrographic surgery. The procedurehas certainly come a long waysince the days of Frederic Mohs andthe application of zinc chloride paste(chemosurgery). Despite the fact that ithas indeed become the “gold standard”for the removal of basal cell carcinoma(BCC) and squamous cell carcinoma(SCC), there remain areas of controversyfor its use in melanoma and otherless common cutaneous neoplasms. Asmore dermatologists (and even a fewnondermatologists) have becometrained and gain experience in this specializedprocedure, and as more communitiesand university teaching centershave established growing Mohs practices,the procedure has become recognizedand embraced by health-careprofessionals and patients alike.

Statins inhibit the activity of the rate-limiting enzyme in the cholesterolbiosynthetic pathway, HMG-CoA reductase, and are widely prescribedfor lowering plasma lipid levels. Several statins have antitumor effects inexperimental models, and observational studies suggest that this anticanceractivity in the laboratory may translate into effective treatments and/orpreventive strategies for certain human cancers. This paper reviews thelaboratory and clinical evidence that statins have anticancer activity, discussesthe possible mechanisms by which tumor growth may be inhibitedby this class of drugs, and outlines strategies for the evaluation of theseagents in the prevention and treatment of human cancers.

Patients having locoregional or metastatic melanoma have a poorprognosis, with 50% to 100% of patients dying from the disease within5 years. Current chemotherapy regimens offer limited benefits to thesepatients, and more effective and less toxic treatments are needed. Wetherefore piloted a study of docetaxel (Taxotere), vinorelbine(Navelbine), granulocyte-macrophage colony-stimulating factor(GM-CSF, sargramostim [Leukine]), or the DVS regimen, in patientswith stage IV melanoma. Eight patients were treated after previousbiochemotherapy and two patients were given the regimen as an initialtreatment. The DVS regimen consisted of docetaxel at 40 mg/m2 IVover 1 hour, vinorelbine at 30 mg/m2 IV over 6 to 10 minutes every 14days, and GM-CSF at 250 mg/m2 SC on days 2 to 12. No grade 3 or 4toxicities were encountered. Of the 10 patients evaluable for response, 5were partial responders (50% response rate). Time to progression for the10 cases ranged from 2 to 26+ months (median: 8 months). The DVSregimen was active against advanced melanoma in both previously treatedand untreated patients. A larger study to confirm the activity of the DVSregimen for stage IV melanoma is currently under way.

Cytokines have been used in the treatment of patients with cutaneousmelanoma. Granulocyte-macrophage colony-stimulating factor(GM-CSF, sargramostim [Leukine]) leads to dendritic cell/macrophagepriming and activation, and also increases interleukin-2 (IL-2)receptor expression on T lymphocytes. IL-2 creates lymphokineactivatedkiller cells and tumor-infiltrating lymphocyte cells. In thisopen-label, single-arm study of 16 high-risk patients, we combined thesetwo agents to take advantage of their different but complementary functions.All patients underwent potentially curative surgery. Postoperatively,each patient received GM-CSF at 125 μg/m2/d subcutaneously(SC) for 14 days; this was followed by IL-2 at 9 million IU/m2/d SC for4 days, and then 10 to 12 days of no treatment. In addition, patientswho had large tumors that could yield over 100 million live tumor cellsreceived autologous melanoma vaccines. The duration of follow-upranged from 21 to 42 months (median: 27 months). During follow-up,five patients developed metastases. This program was carried out on anoutpatient basis, and no hospitalization was required. It was well toleratedwith minimal side effects. The combination treatment regimen ofGM-CSF and IL-2 with or without autologous vaccine used adjuvantlyappears to benefit high-risk melanoma patients; further clinical testingof this regimen is warranted.

Granulocyte-macrophage colony-stimulating factor (GM-CSF,sargramostim [Leukine]) is a powerful cytokine that is able to stimulatethe generation of dendritic cells. Adjuvant treatment with continuous lowdoseGM-CSF has been shown to prolong survival of stage III/IV melanomapatients. Data on continuous low-dose GM-CSF therapy in tumorsother than prostate cancer are still lacking.

Cutaneous malignant melanoma is a relatively common neoplasm. In the United States in 1995, an estimated 34,000 cases of melanoma will be diagnosed, and 7,200 persons will die of melanoma [1]. Early primary melanoma is highly curable, but once the disease becomes disseminated, it is nearly always fatal. The overall survival rate has more than doubled from 40% in the 1960s to more than 80% today, but this increase is attributable to earlier diagnosis rather than to treatment advances [2].

Combined-modality positronemissiontomography (PET)–computed tomography (CT) isbecoming the imaging method ofchoice for an increasing number ofoncology indications. The goal of thispaper is to review the evidence-basedliterature justifying PET-CT fusion.The best evidence comes from prospectivestudies of integrated PETCTscans compared to other methodsof acquiring images, with histopathologicconfirmation of disease presenceor absence. Unfortunately, veryfew studies provide this kind of data.Retrospective studies with similarcomparisons can be used to provideevidence favoring the use of integratedPET-CT scans in specific clinicalsituations. Also, inferential conclusionscan be drawn from studies whereclinical rather than pathologic dataare used to establish disease presenceor absence.

Vaccines are a promising but still experimental treatment for melanoma.They are intended to stimulate immune responses against melanomaand by so doing, increase resistance against and slow the progressionof this cancer. Key requirements for vaccines to be effectiveare that they contain antigens that can stimulate tumor-protective immuneresponses and that some of these antigens are present on thetumor to be treated. Unfortunately, these antigens are still not known.To circumvent this problem, polyvalent vaccines can be constructedcontaining a broad array of melanoma-associated antigens. Severalstrategies are available to construct such polyvalent vaccines; each hasadvantages and disadvantages. Clinical trials have shown that vaccinesare safe to use and have much less toxicity than current therapy formelanoma. Vaccines can stimulate both antibody and T-cell responsesagainst melanoma, with the type of response induced, its frequency,and its magnitude depending on the vaccine and the adjuvant agentused. A growing body of evidence suggests that vaccines can be clinicallyeffective. This evidence includes correlations between vaccineinducedantibody or T-cell responses and improved clinical outcome,clearance of melanoma markers from the circulation, improved survivalcompared to historical controls, and most convincingly, two randomizedtrials in which the recurrence-free survival of vaccine-treatedpatients was significantly longer than that of control groups.

There have been an astoundingnumber of published reviewson human cancer vaccines, andI take responsibility for my share. Apparentlythe interest of the medicalcommunity in cancer vaccines remainsintense, despite the modest progressthat has been made in our field and thepaucity of convincing, positive clinicalresults. Somehow the idea of treatinga cancer by inducing an antitumorimmune response or strengthening theexisting one is strongly appealing bothto physicians and to patients. Whetherthis enthusiasm is justified by the scienceis a question that should troublethe sleep of all of us who call ourselvestumor immunologists.