Saturday, January 3, 2009

Adjuvant Therapy in Melanoma: New Combination Cytokine and Other Strategies


Melanoma is the leading cause of death among all types of skin cancer and is the fifth most common type of cancer in men in the United States. The incidence of melanoma is increasing; in 2008, the incidence of this disease is expected to exceed 60,000, with 8000 deaths.[1] Fortunately, up to 95% of patients will present with either local or regional disease, which is potentially curable.[2] Although the causes of this increased incidence of melanoma are debated, it is thought that increased exposure to ultraviolet radiation interacts in some manner with genetic factors to initiate melanoma.[3]

Histologically, melanoma is characterized by proliferation of transformed melanocytes.[4] These long-lived cells are normally present at the dermo-epidermal junction and impart pigment to the skin; they are typically resistant to DNA damage and apoptosis, a characteristic of melanoma as well. The principal subtypes of cutaneous melanoma are superficial spreading, nodular, lentigo maligna, and acral lentiginous; rarer noncutaneous primary sites include the mucosal membranes and the pigmented epithelium of the eye. Most types of melanoma are more common among whites, although acral lentiginous melanoma occurs with equal frequency in nonwhites.

Several pathologic and clinical factors are predictive of the risk of recurrence and death in persons with melanoma. The clinical factors include age, sex, location, and lymph node or distant organ involvement, whereas pathologically, the tumor depth (Breslow depth), ulceration, mitotic rate, and presence of microsatellites can determine the risk for recurrence or spread.[5] The recent revision of the American Joint Committee on Cancer staging system for melanoma incorporates many of these factors. Some pathologic features, such as involvement of skin layers (Clark levels) and the presence of tumor regression, have not stood up to rigorous multivariate analysis and are no longer used clinically to determine the risk for recurrence or the current staging classification.[6] Over 60% of melanomas have mutations in the B-type RAF-1 kinase (BRAF).[7,8] About 80% of these mutations are found at exon 15, at a single amino acid residue, usually a substitution for valine by glutamic acid, V599E (now referred to as V600E). This mutation causes increased kinase activation and signaling through the mitogen-activated protein (MAP) kinase pathway.[9,10] Surprisingly, this event occurs with high frequency in benign nevi as well as in melanoma.[11] An additional 15% to 20% of melanomas have mutations in N-Ras, which lies upstream of BRAF.[12] Both of these genes code for proteins that are part of the ERK-MAP kinase pathway. A small proportion of melanomas, especially those originating in sun-damaged skin, the palms and soles, and mucous membranes, have mutations or amplifications in the c-kit gene.[13]

Recent reports suggest that integration of molecular profiling with pathologic and clinical features may result in a better prognostic profile and help to more precisely determine an individual's risk for recurrence.[14] It has been suggested, for example, that the melanoma arising from sun-exposed skin in older persons is more likely to have c-kit mutations than the truncal melanoma arising in younger patients, which is more likely to have BRAF mutations.[14]
Surgical excision with wide margins and sentinel lymph node biopsy (for a melanoma whose depth is ≥ 1 mm) is the treatment of choice for primary melanoma. Several large clinical trials have helped to define the width of margins needed to resect melanoma and reduce the risk for recurrence.[15-17]

Currently, melanoma of ≤ 1 mm thickness is resected with surgical margins of 1 cm, whereas melanoma ≥ 2 mm is resected with margins of 2 cm, and intermediate-thickness melanoma is resected with 1- to 2-cm margins. Mapping the draining sentinel lymph node with use of a tracer and careful histologic examination of this node is now a standard of care for melanoma ≥ 1 mm in thickness.[18] High-risk melanoma, defined as stages IIB, IIC, and III, often recurs after excision and is associated with a 40% to 80% chance of death.[2] Given the high risk for recurrence (and subsequent mortality), there is an obvious need for reduction of recurrence risk. This review will address several treatment approaches that have been employed as adjuvant therapy following primary surgical excision.

Interferon Therapy

The interferons (IFNs) can produce antitumor effects through upregulation of the immune system. In humans, IFNs are structurally divided into 2 classes: type I and type II. The type I family, which is used clinically for the treatment of several diseases, includes alpha (alfa), beta, and omega; the type II family has only 1 member, IFN gamma. The various subtypes are further subdivided for pharmaceutical preparations, eg, IFN alfa-2a, IFN gamma-1b.[19] IFNs can stimulate both the innate and adaptive arms of the immune system; for example, they can enhance major histocompatibility complex (MHC) class I antigen presentation, increasing innate immunity and maturation of dendritic cells and leading to enhanced adaptive immunity. They also have antiangiogenic and direct cytotoxic effects on some malignant cells. However, the exact mechanism by which they produce antitumor effects is unclear.
Two large randomized trials have shown that high-dose IFN-alfa-2b significantly reduces the risk for recurrence compared with observation alone in patients with resected cutaneous melanoma.[20,21] A third large randomized trial has shown a significant improvement in overall survival with high-dose IFN-alfa-2b compared with the GM2 ganglioside conjugated to keyhole limpet hemocyanin (KLH) melanoma vaccine in patients with resected stage IIB-III melanoma.[22] In the first trial, ECOG 1684, patients with thick primary melanoma (≥ 4 mm depth) or lymph node-positive disease were randomized to receive IFN-alfa-2b 20 MIU/m2/day intravenously for 4 weeks followed by 10 MIU/m2 subcutaneously 3 times per week for 48 weeks or to observation. Patients who received IFN-alfa-2b had improved relapse-free survival (RFS) (5-year RFS 37% vs 26%; P = .0023) and overall survival (OS) (5-year OS 46% vs 37%; P = .0237) compared with the observation arm. This led to the approval by the US Food and Drug Administration of IFN-alfa-2b for the treatment of high-risk melanoma after surgical resection. Because this high dose appeared to be effective, the next ECOG trial was conducted to determine whether a lower dose of IFN might be as effective as that studied in ECOG 1684. Therefore, ECOG 1690 randomized patients with thick or node-positive melanoma to 1 of 3 arms: (1) high-dose IFN-alfa-2b (20 MIU/m2/day intravenously for 4 weeks followed by 10 MIU/m2 subcutaneously 3 times per week for 48 weeks) for 1 year; (2) low-dose IFN-alfa-2b (3 MIU/m2 3 times per week subcutaneously for 2 years); and (3) observation. Five-year RFS in the 3 arms was 44%, 40%, and 35%, respectively. The difference between high-dose IFN and observation was statistically significant (P = .05), but the difference between low-dose IFN and observation was not. Of note, no improvement in overall survival was noted between either of the treatment arms and observation.
The GM2 ganglioside vaccine had shown promising results in small phase 1 and 2 trials and was brought forward for further clinical testing.[23,24] The gangliosides are complex carbohydrates found on the outer cell membrane that can be as immunogenic as protein antigens. The resulting trial, ECOG 1694,[22] was different from the 2 prior studies because it compared high-dose IFN to GM2-KLH/21 vaccine in patients with resected stage IIB and III melanoma. High-dose IFN improved both RFS (hazard ratio [HR] 1.49; P = .00045) and OS (HR 1.38; P = .023) compared with GM2 vaccine, and this trial was halted early by the data safety monitoring committee. The benefit attributed to IFN was seen in patients with node-positive disease as well as those with node-negative disease.

Because the findings of these trials and others conducted by European and American investigators were inconsistent, several meta-analyses have been performed to assess the data globally. An authoritative meta-analysis performed by Wheatley and colleagues[25] examined 12 randomized controlled trials and found that RFS was highly significantly improved with IFN-alfa by 17% (HR 0.83; P = .000003). The benefit on OS associated with IFN-alfa trended toward a 7% improvement but was not statistically significant (HR 0.93; confidence interval [CI], 0.85-1.02; P = .1). The investigators subsequently have updated their meta-analysis and shown a slightly better outcome for IFN-alfa in terms of OS.
Inasmuch as IFN-alfa has a short half-life necessitating frequent injection and resulting in side effects from rapid variation in blood levels, it has been modified to reduce clearance and increase its half-life.[19] One such modification is the addition of a 12,000-dalton polyethylene glycol chain, which results in pegylated IFN (PEG-IFN). In the treatment of viral hepatitis, PEG-IFN appears to be as efficacious as IFN with reduced toxicity.[26] To determine whether PEG-IFN was effective in melanoma, the European Organization for Research and Treatment of Cancer (EORTC) conducted a large trial, EORTC 18991, which randomized more than 1300 patients with node-positive melanoma postoperatively to either PEG-IFN for a maximum of 5 years or observation. The 4-year RFS was 45.6% and 35.9% (P = .01) in the PEG-IFN and observation groups, respectively. No difference in OS was noted.[27] The greatest benefit appeared to be in patients with microscopic nodal disease. Overall, patients appeared to tolerate this treatment relatively well.
The major issue limiting the use of IFN in patients with melanoma has been its toxicity. IFN is associated with a characteristic and sometimes debilitating constellation of signs and symptoms that can make its use challenging.

Commonly, patients experience fatigue, myalgia, anorexia, altered taste sensation, fevers, chills, loss of concentration and short-term memory, and other neuropsychiatric abnormalities. Significant depression has been reported in some patients. Laboratory abnormalities associated with use of IFN include elevations in transaminase levels, neutropenia and thrombocytopenia, increased creatinine levels, and anemia. Commonly, patients are dehydrated and need to be encouraged to increase their fluid intake and maintain their activity levels. Given the modest benefit of IFN in terms of reducing the risk for recurrence and death from melanoma, its significant toxicity profile has made it an option for only a select subpopulation of patients at high risk for melanoma recurrence.[19]
Granulocyte-Macrophage - Colony-Stimulating Factor

Although granulocyte-macrophage - colony-stimulating factor (GM-CSF; sargramostim) was initially identified as a colony-stimulating factor for myeloid cells in the bone marrow, it was also found to induce differentiation of dendritic cells (DCs).[28] The DCs, sometimes referred to as antigen-presenting cells, display tumor antigens to the immune system in the appropriate context and are increasingly recognized as a vital afferent arm of the immune system. Both quantitative and functional defects in DCs have been described in patients with cancer. These defects may contribute to "tumor escape" of immune surveillance. Specifically, GM-CSF increases the mobilization, differentiation, and function of DCs[29,30] and hence enhanced antigen presentation to CD4 and CD8 T cells.
GM-CSF appeared to be effective in increasing tumor-specific immunity when used as an adjuvant for vaccines.[30] In the metastatic disease setting, GM-CSF has been injected intralesionally and intrahepatically (with use of a hepatic artery catheter) and administered as an inhalational treatment. A GM-CSF-producing adenovirus appears to induce regression of metastatic melanoma when injected into lesions.[31] GM-CSF inhaled as an aerosol resulted in regression of pulmonary metastasis from melanoma in a phase 1 study.[32] In a phase 1 study of patients with metastatic melanoma, a 32% response rate was noted in patients with liver metastases following hepatic arterial infusion of large doses of GM-CSF.[33]
On the basis of these data, Spitler and colleagues[34] evaluated the role of GM-CSF in patients with high-risk (stage IIIB, IIIC, or IV) resected melanoma. Patients received GM-CSF 125 µg/m2 subcutaneously daily for 2 weeks every month for 1 year. The median survival of patients in this study was 37.5 months and far exceeded the median survival of 12.2 months in historical controls. The limitations of the study included the lack of a placebo arm and heterogeneity between the historical control and study groups. Overall, GM-CSF was well tolerated.
To confirm the findings of this trial and to examine the effect of GM-CSF on DCs, Daud and coworkers conducted a study with essentially the same dose and schedule in a similar patient population.[35,36] OS and RFS were 65 months and 5.6 months, respectively. GM-CSF treatment caused an increase in mature DCs, first identified after 2 weeks of treatment and normalizing by 4 weeks. Patients with decreased DCs at baseline had significant increases in DC number and function compared with those with "normal" parameters at baseline (Figure 1).[36] No change was observed in the number of myeloid-derived suppressor cells (MDSCs). Early recurrence (< 90 days) correlated with a decreased effect of GM-CSF on host DCs, compared with late or no (evidence of) recurrence (Figure 2).[36] Therefore, greater increase of DCs was associated with remission or delayed recurrence. Although this study lacked a control group, the survival data for the GM-CSF-treated patients does appear impressive. The benefits of GM-CSF appear to be greater in those with reduced DCs, but inasmuch as these analyses were exploratory, further investigation is warranted.
GM-CSF is currently being actively investigated in combination with other immunologic agents and chemotherapy. GM-CSF with the anti-CTLA-4 antibody ipilumimab has been explored in a phase 1 trial[37] (L. Fong, personal communication) and has shown some promising activity in prostate cancer. In addition, it has been explored as a component of combination therapy[38-40] and also as a maintenance or consolidation regimen in patients with metastatic melanoma who have benefited to some extent from chemotherapy.[41] There is also an ongoing trial with high-dose IL-2 in combination with GM-CSF (J. Lutzky, personal communication).

Anti-CTLA-4 Antibodies

The use of monoclonal antibodies to inhibit cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is a novel strategy in melanoma. These antibodies have been found to induce tumor regression and improve long-term survival in tumor-bearing mice.[42-44] Early preclinical studies showed that CTLA-4 serves as a natural braking mechanism for T-cell activation, allowing a return to homeostasis after an immune response. Inhibition of CTLA-4 upregulates several downstream targets, including T helper (Th) 1- and 2- produced cytokines (ie, interleukin 1 and 2) and cell cycle machinery (CDK-4, cyclin D3), leading to a more robust antitumor immune response. Two anti-CTLA-4 antibodies are currently in phase 2 and 3 trials: ipilimumab (also known as MDX-010) and tremelimumab (also known as CP 675,206).
Prolonged, but sometimes delayed, responses have been seen in patients with melanoma who have received either of the anti-CTLA-4 antibodies.[45,46] Similar to the effect seen with IFN therapy, immune-related adverse events correlate with more positive outcomes in patients with metastatic melanoma who receive anti-CTLA-4 therapy, including prolonged time to relapse.[47] Recently, it has been reported that tremelimumab was no better than standard dacarbazine (DTIC) or temozolomide for the up-front treatment of metastatic melanoma.[48] Results of an ongoing trial of ipilimumab and DTIC vs DTIC alone in the setting of metastatic melanoma are expected soon. Because anti-CTLA-4 antibodies appear to be effective in the phase 2 setting in metastatic disease, they are also being considered for use in the adjuvant setting. Currently, an ongoing EORTC study is examining ipilimumab vs observation in patients with high-risk melanoma, and combinations of anti-CTLA-4 antibody with GM-CSF and IFN are promising for evaluation because different parts of the immune system may be stimulated.


Tumor cells can express novel antigens or quantitatively different antigens compared with "normal" or nondividing cells. Harnessing the immune system to destroy malignant cells by recognizing these antigens is a major goal of tumor immunotherapy. Tumor antigens upregulated in melanoma include MART-1 (Melan A), gp100, and tyrosinase; other investigators have focused on the cancer-testis antigens, which are upregulated in tumor cells but present only in human germ cells in the body. Although early studies of therapeutic vaccines against melanoma showed some promise, [49,50] randomized, prospective, placebo-controlled clinical trials have failed to prove a benefit. An allogeneic melanoma vaccine not only failed to improve either DFS or OS, but the study arm actually showed worsened survival.[51] Similarly, although the GM2 ganglioside vaccine showed promise in phase 2 trials,[23] a recent randomized study showed worsened survival in the vaccine population compared with an observation group.[52] Although these signals may be confined to these particular vaccines and not necessarily to peptide or DC vaccines, caution is needed when interpreting vaccine studies given these data.


Historically, DTIC has been the standard chemotherapy for patients with high-risk melanoma.[53] The use of chemotherapy in the adjuvant setting in melanoma has been tested in randomized trials and has shown no benefit.[54-56] At this time, chemotherapy should not be administered in the adjuvant setting outside of a clinical trial. Whether chemotherapeutic agents may be effective when used in combination with immune-modulating agents is still under investigation.

Other Novel Therapies

As more details are elucidated about the biology of melanoma, new pharmacologic targets are being identified. Among these are immunologic targets such as programmed death (PD)-1, anti-CD40, and anti-41BB (CD137) antibodies, which are currently in phase 1 and 2 trials.[35] PD-1, a member of the tumor necrosis factor family, has shown promising results in murine trials and is currently in phase 1 investigation. CD40 is a receptor expressed on B cells and DCs; it is bound by CD40 ligand found on activated T cells. Phase 1 trials[57] have demonstrated a modest dose-related benefit (0.3 vs 0.2 mg/kg) that has prompted ongoing phase 2 trials. Also under investigation is adoptive cell transfer after lymphoid depletion (homeostatic lymphoid proliferation).[58] A very interesting proof-of-concept study showed that CD4 T cells directed against NY-ESO-1 antigen were able to produce a response in melanoma.[59]
Targeted agents directed against a growth pathway specific to melanoma are also in development. Sorafenib, a multikinase inhibitor with multiple targets including VEGF, has had modest activity when studied as monotherapy, with a 19% rate of stable disease.[60,61] Src inhibitors such as dasatinib, VEGF kinase antagonists such as sunitinib, and c-kit inhibitors such as imatinib are all under investigation in melanoma.[62].Although these agents are currently not known to be effective in the metastatic setting, they may hold promise for early-stage disease.


Currently, only a few adjuvant therapies show any effectiveness in terms of decreasing the mortality rate in patients with high-risk melanoma. IFN is the only agent that has been proven to reduce recurrences after surgery, although its benefit on survival is likely very modest. However, this modest benefit must be weighed against the toxicities, and hence candidates for adjuvant IFN therapy must be chosen carefully.
Among the newer agents, GM-CSF shows promise: two phase 2 studies have shown that GM-CSF administered subcutaneously may be associated with prolonged survival. Currently a major randomized trial is under way to determine the degree, if any, of this benefit. The combination of GM-CSF with other immune modifiers, such as anti-CTLA-4 antibody or IFN, may be the next step in clinical trials, although no trial data are yet available with these combinations. Vaccines have an extensive history in melanoma, but to date no vaccine preparation has shown a survival or recurrence benefit in melanoma, and recent data even indicate a potential for harm. Other agents are on the horizon, including targeted therapies directed toward the specific mutations present in certain melanomas, which could be used in the adjuvant setting. Some exciting cell-based therapies have been shown to work in proof-of-concept clinical trials; more data are awaited prior to studying these agents in the adjuvant setting.

This activity is supported by an independent educational grant from Bayer HealthCare Pharmaceuticals.

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Greetings to One and All

This Blog is dedicated My Brother Kenny B. who passed away in the late 1970's with Cancer before the Internet.

It was he, who showed me How to live and give back. He was wise beyond his years.

Kenny B

Jimmy and Dee

Carepage: Jimmybreitfeller
Jimmy Breitfeller

My Profile as of 2009

My photo
Last July (2005)I was riding my bicycle to work at the Eastman Kodak Research Labs about 3 miles from home. I was wearing a knapsack to carry my things to and from the labs. I started noticing an ache on my back. So I decide to go to the dermatologist. To make the long story short, it was cancer. I knew from my research that I would be needing adjuvant therapy. So I started communicating with Sloan Kettering, University of Pittsburgh Cancer Center, and a couple of others including the Wilmot Cancer Center at Strong. I realized that by telling my story, I might help someone else out there in a similar situation. So to all who are linked by diagnosis or by relation to someone with melanoma, I wish you well. Stay positive, read as much as you can (information helps to eliminate the fear associated with the unknown), and live for today, as no one can predict what tomorrow may bring. Jimmy B. posted 12/15/08


The information contained within this Blog is not meant to replace the examination or advice of your Oncologist or Medical Team. The educational material that is covered here or Linked to, does not cover every detail of each disorder discussed.

Only your physician/Oncologist can make medical decisions and treatment plans that are appropriate for you. But, An Educated Consumer is a Smart consumer.

As Dr. Casey Culberson Said:

"The BEST melanoma patient is an ACTIVE PARTICIPANT in his or her treatment

Melanoma and the “Magic Bullet” (Monoclonal Antibodies)

Just to let you know I posted the first draft of the Melanoma and the “Magic Bullet” (Monoclonal Antibodies). on Melanoma Missionary In the Shared File Section. you can download it for 19.95 (Only kidding) it is Free for the taking.

It is 33 pages long and may help you in your quest for the Yellow Brick Broad. Just to let you know it is only the first draft. Revisions are sure to come. I wanted to get it to the people that need it the most, the Melanoma Patients.


So, where does Interluekin-2 (IL-2) come into play? According to Byung-Scok et al and recent reports, IL-2 is not needed for developmental CD4+ CD25+ Treg cells in the thymus but does play an important role in the maintenance and function in the peripheral.18 Peripheral is defines as secondary system outside the bone marrow and thymus. It entails the site of antigen, immune system interaction. IL-2 is required for the peripheral generation of Tregs based Abbas’s and colleagues research.19

IL-2 prevents the spontaneous apoptosis of the CD4+ CD25+ Treg cells. It has been reported that patients with multiple advance-stage tumors have elevated levels of Tregs within the tumor microenviroment.20 Interluekin-2 is the survival factor for CD4+ CD25+ Treg cells.21 If the addition of IL-2 is on or before the maximum propagation of the CD4+ T cells, the Tregs population can increase 5-fold in a 96 hour period based on certain growth mediums.

By controlling the addition of the endogenous IL-2, one has a knob to turn and can lead to the control of the expansion of the Tregs. When you combined this control with the anti-CTLA-4 blockage, you can shift the balance of the immune response.

Now here is the catch. The maintenance and function of the CD8+ T-cells require CD4+ cells which secrete IL-2. So we don’t want to deplete the CD4+ cells, we want to control the expansion of the Tregs which are a subset of the CD4+ cells. It has been postulated by some researchers that the Anti-CTLA-4 blockage also suppresses the Treg function in a different mechanism. By using IL-2 as the rate limiting factor, we can suppress the CD4+ CD25+ Treg cell expansion by controlling the concentration and timing of the Inerluekin-2 at the tumor microenvironment.

The Interluekin-2 plays another role in this Melanoma Maze. In a study by Janas et al, Il-2 increases the expressions of the perforin and granzyme A, B and C genes in the CD8+ T-cells. This increase expression causes the CD8+ T-cells to mature into Cytoxic T Lymphocytes (CTLs). The exogenous IL-2 is required for the granzyme proteins. As stated previously, CTLs have cytoplasmic granules that contain the proteins perforin and granzymes. A dozen or more perforin molecules insert themselves into the plasma membrane of target cells forming a pore that enables granzymes to enter the cell. Once in the tumor cell, these enzymes are able to breakup (lyse) the cell and destroy it. This is the beginning of the end for the cancer cells. The tumors begin to shrink and the rest is history,

On the other hand, prolong therapy with Il-2 can result in causing apoptotic death of the tumor- specific CD8+ T-cells.23

Clearly in a clinical setting, timing, dose, and exposure to these drugs play a major roll in the immunotherapy, and can have dramatic effects on the outcome.

All it takes is that one magic bullet to start the immune reaction..

Melanoma And The Magic Bullet (Monoclonal Antibodies)

Public Service Announcement

A call for Melanoma Patients by Dr. Steven A Rosenberg

"We continue to see a high rate of clinical responses in our cell transfer immunotherapy treatments for patients with metastatic melanoma", Dr. Rosenberg said.

"We are actively seeking patients for these trials and any note of that on a patient-directed web site would be appreciated."

If you would like to apply for his trials, here is the website and information.

Dr. Rosenberg's information

Dr. Rosenberg's Clinical Trials

For the Warriors

The Melanoma Research Alliance has partnered with Bruce Springsteen, the E Street Band, and the Federici family to alleviate suffering and death from melanoma. Please view Bruce Springsteen’s public service announcement inspired by Danny Federici. Danny was the E Street Band’s organist and keyboard player. He died on April 17, 2008 at Memorial Sloan-Kettering Cancer Center in New York City after a three year battle with melanoma.

Source Fastcures blog

Join the Relay for Life!!!


Dear Family and Friends,

I’ve decided to take a stand and fight back against cancer by participating in the American Cancer Society Relay For Life® event right here in my community! Please support me in this important cause by making a secure, tax-deductible donation online using the link below.

To donate on line now, click here to visit my personal page.
Jimmy B AKA Melanoma_Missionary

Relay For Life® is a life-changing event that brings together more than 3.5 million people worldwide to:

CELEBRATE the lives of those who have battled cancer. The strength of survivors inspires others to continue to fight.

REMEMBER loved ones lost to the disease. At Relay, people who have walked alongside people battling cancer can grieve and find healing.

FIGHT BACK. We Relay because we have been touched by cancer and desperately want to put an end to the disease.

Whatever you can give will help - it all adds up! I greatly appreciate your support and will keep you posted on my progress.

Keep the Fire Burning!!!



Jimmy Breitfeller
Turn off Music before you "Click to Play"
Signs of Melanoma Carcinoma Skin Cancer

How Skin Cancer Develops by " : Dermatology"

Call for Patients with Unresectable Liver Metastases Due to Melanoma

Delcath Systems Granted Orphan-Drug Designations for Cutaneous and Ocular Melanoma

Delcath is actively enrolling patients in a Phase III clinical trial testing its proprietary drug delivery system, known as Percutaneous Hepatic Perfusion (“PHP”), with melphalan for the treatment of ocular and cutaneous melanoma metastatic to the liver.

This NCI-led trial is enrolling patients at leading cancer centers throughout the United States. Commenting on these orphan-drug designations, Richard L. Taney, President and CEO of Delcath, stated, “These favorable designations are important steps in our efforts to secure Delcath’s commercial position upon conclusion of our pivotal Phase III trial for metastatic melanoma. We remain steadfast in our commitment to become the leader in the regional treatment of liver cancers and we continue to enroll patients in this study, and advance our technology and the promise that it offers to patients with these deadly forms of melanoma and other cancers of the liver, all with limited treatment options.”

Orphan drug designation, when granted by the FDA’s Office of Orphan Products Development, allows for up to seven years of market exclusivity upon FDA approval, as well as clinical study incentives, study design assistance, waivers of certain FDA user fees, and potential tax credits.

Current Trial Centers

Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using
Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies

James F. Pingpank, Jr., MD, FACS
Associate Professor of Surgery
Division of Surgical Oncology
Suite 406, UPMC Cancer Pavillion
5150 Centre Avenue
Pittsburgh, PA 15232
412-692-2852 (Office)
412-692-2520 (Fax)

Blog Archive

Call For Melanoma Patients!!!!

Call For Melanoma Patients!!!!

Dr. Rosenberg Has a New Clinical Trial.

Our latest treatment has a 72% objective response rate with 36% complete responses.

We are currently recruiting patients for our latest trial.

Is there some way to post this “Call for Patients” on the web site?

Steve Rosenberg

Dr. Rosenberg's Clinical Trials

(For a copy of the research paper.. see My Shared files)

The news headlines shown above for Melanoma / Skin Cancer are provided courtesy of Medical News Today.