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D Schadendorf

Publications and source records attributed to D Schadendorf.

At least 73 records · Page 4Linked to original sources
PubMed1999

Search for novel proteins involved in the development of chemoresistance in colorectal cancer and fibrosarcoma cells in vitro using two-dimensional electrophoresis, mass spectrometry and microsequencing.

In search of novel mechanisms that may lead to the development of chemoresistance of malignant tumors of the large bowel we used two-dimensional electrophoresis to identify proteins that were overexpressed in colorectal and fibrosarcoma cell lines that were resistant towards mitoxantrone. This cytostatic drug is known to lead to atypical multidrug resistance, i.e., the classical mechanism of multidrug resistance (MDR) accompanied by the overexpression of P-glycoprotein (P-gp) is ineffective. Using mass spectrometry and microsequencing we found adenine phosphoribosyl transferase and breast cancer specific gene 1 (BCSG1) overexpressed in the resistant colorectal tumor cell line. In the chemoresistant fibrosarcoma cell line we found two proteins that were overexpressed. One was identified as Rho-guanine dinucleotide phosphate (Rho-GDP) dissociation inhibitor and the other had sequence homologies with yeast protein yer-7. The putative role of these proteins is discussed.

Antineoplastic Agents↗
PubMed1999

Cell-based vaccination against melanoma--background, preliminary results, and perspective.

Melanoma is the prototype of a tumor to which many forms of immunotherapy have been applied extensively over the past two decades. Melanoma vaccines (active specific immunotherapy) are designed to modulate the immune system and have subsequent anti-tumor effects with minimal toxicity. Previous attempts to produce melanoma vaccines include immunization with whole tumor cells/cell lysates admixed with nonspecific adjuvants. While these vaccines generate enhanced anti-tumor immunity in a subset of patients, some of whom survive for longer than historical controls, no clinical benefit has so far been demonstrated in a properly controlled phase III study. Genetic modifications of tumor cells to make them express cytokines afford new-generation melanoma vaccines, and generate long-lasting systemic antitumor immunity in animal models. Translation of these preclinical results primarily into melanoma patients with advanced diseases shows the potential to induce systemic antitumor immune responses and in some instances tumor regression with acceptably low toxicity. The efficacy of this novel vaccine approach would be expected to be higher when used in a postsurgical adjuvant setting when the tumor load is small. Other novel vaccine approaches such as dendritic cell-based therapy also hold promise for the treatment of melanoma. The clinical value of all these new approaches will eventually have to be established in prospectively randomized clinical studies.

Animals↗
PubMed1999

The chemokine RANTES is secreted by human melanoma cells and is associated with enhanced tumour formation in nude mice.

Modulation of tumour cell growth by tumour-infiltrating leucocytes is of high importance for the biological behaviour of malignant neoplasms. In melanoma, tumour-associated macrophages (TAM) and tumour-infiltrating lymphocytes (TIL) are of particular interest as inhibitors or enhancers of cell growth. Recruitment of leucocytes from the peripheral blood into the tumour site is mediated predominantly by chemotaxins, particularly by the group of chemokines. The aim of this study was to identify peptides released by human melanoma cells with monocyte chemotactic properties. To assure the presence of biologically active mediators, biochemical purification and biological characterization of peptides was based on a detection system dependent on bioactive, monocyte chemotactic activity in vitro. Cell culture supernatants of melanoma cells were fractioned by heparin-sepharose followed by preparative reversed-phase HPLC steps to enrich monocyte chemotactic activity in one single band on a sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) gel. These purified fractions were shown to react with RANTES-specific antibodies in an enzyme-linked immunosorbent assay (ELISA) as well as in Western blot analysis. Amino acid sequencing of the N-terminal protein fragment confirmed 100% homology to the RANTES protein. Further analysis showed that four out of eight melanoma cell lines constitutively expressed and secreted the beta-chemokine RANTES as detected by ELISA. The amount of RANTES protein secreted (up to 50 ng ml(-1)) was about 5-50 times higher than interleukin 8 (IL-8), determined in the same supernatant samples. Tumour necrosis factor alpha, (TNF-alpha), not, however, IL-2, interferon-gamma (IFN-gamma), or (alpha-melanocyte-stimulating hormone (alpha-MSH) was able to up-regulate RANTES and interleukin 8 secretion. Furthermore, higher levels of RANTES secretion in vitro were associated with increased tumour formation upon s.c. injection of six human melanoma cell lines in nude mice. Our data provide evidence that a subset of melanoma cells express mRNA and secrete RANTES protein which may be partly responsible for the recruitment of monocytes, T-cells and dendritic cells into the tumours. However, transplantation experiments in nude mice suggest that effects of RANTES may also benefit tumour progression. Further studies are needed to dissect the underlying mechanisms.

Animals↗
PubMed1999

In vivo selective expansion of a tumour-specific cytotoxic T-cell clone derived from peripheral blood of a melanoma patient after vaccination with gene-modified autologous tumour cells.

Melanoma-specific cytotoxic T lymphocytes (CTL) can be generated from peripheral blood lymphocytes (PBL) by mixed lymphocyte-tumour cell cultures. Analysis of CTL precursor frequencies in peripheral blood of melanoma patients is generally used for immunomonitoring purposes to evaluate vaccination efficacy. At present, it is unclear whether PBL-derived CTL generated in vitro are indicative of an anti-tumour immune response in vivo. Three tumour-specific human leucocyte antigen (HLA)-B/C-restricted CTL clones were derived from peripheral blood of a melanoma patient immunized with interleukin-7 (IL-7) gene-modified tumour cells. CTL clones differing in their T-cell receptor-gamma (TCRgamma) rearrangement produced interferon-gamma, IL-4 and/or IL-10. On the basis of their unique TCRgamma gene rearrangements clone-specific primers were generated for detection of clone-specific DNA by polymerase chain reaction. One CTL clone (E5) of the three was found to be selectively expanded in one of seven metastases obtained at autopsy, as determined by Southern blot hybridization. However, the presence of E5 in only one of seven metastases at death indicates that the in vivo accumulation of the specific CTL clone was not sufficient to contain tumour progression. Nevertheless, our data support the proposition that analysis of anti-tumour activity of PBL-derived CTLs may reflect an anti-tumour immune response in vivo.

Blotting, Southern↗
PubMed1999

Association of genomic imbalances with resistance to therapeutic drugs in human melanoma cell lines.

The reason why human malignant melanomas respond poorly to chemotherapy is not known. In an attempt to identify genes responsible for such resistance or sensitivity to therapeutic drugs, we studied the parental human melanoma cell line MeWo, as well as eight drug-resistant sublines of MeWo. These have low and high levels of resistance to four chemotherapeutic drugs with different modes of action: Vindesine, cisplatin, fotemustine and etoposide. Comparative genomic hybridizations with genomic DNA from these cell lines as probes revealed a number of chromosome gains and losses which occurred upon selective pressure during development of the sublines. The MeWo subline with high resistance to the topoisomerase II inhibitor, etoposide, exhibited the highest number of acquired chromosome imbalances. Interestingly, the two lines with high resistance to cisplatin and fotemustine, respectively, shared three additional imbalances, loss of 9p, loss of distal 12p and gain on distal 15q. The importance of these coincident imbalances is discussed.

Aneuploidy↗
PubMed1998

Increased expression of annexin I and thioredoxin detected by two-dimensional gel electrophoresis of drug resistant human stomach cancer cells.

The therapy of advanced cancer using chemotherapy alone or in combination with radiation or hyperthermia yields an overall response rate of about 20-50%. This success is often marred by the development of resistance to cytostatic drugs. Our aim was to study the global analysis of protein expression in the development of chemoresistance in vitro. We therefore used a cell culture model derived from the gastric carcinoma cell line EPG 85-257P. A classical multidrug-resistant subline EPG85-257RDB selected to daunorubicin and an atypical multidrug-resistant cell variant EPG85-257RNOV selected to mitoxantrone, were analysed using two-dimensional electrophoresis in immobilized pH-gradients (pH 4.0-8.0) in the first dimension and linear polyacrylamide gels (12%) in the second dimension. After staining with coomassie brilliant blue, image analysis was performed using the PDQuest system. Spots of interest were isolated using preparative two-dimensional electrophoresis and subjected to microsequencing. A total of 241 spots from the EPG85-257RDB-standard and 289 spots from the EPG85-257RNOV-standard could be matched to the EPG85-257P-standard. Microsequencing after enzymatic hydrolysis in gel, mass spectrometric data and sequencing of the peptides after their fractionation using microbore HPLC identified that two proteins annexin I and thioredoxin were overexpressed in chemoresistant cell lines. Annexin I was present in both the classical and the atypical multidrug-resistant cells. Thioredoxin was found to be overexpressed only in the atypical multidrug-resistant cell line.

Annexin A1↗
PubMed1998

Expression and functional activity of the IL-8 receptor type CXCR1 and CXCR2 on human mast cells.

To further elucidate mechanisms involved in mast cell accumulation at sites of cutaneous inflammation, we have studied the ability of human leukemic mast cells (HMC-1 cells) to express functionally active IL-8 receptors. Expression of mRNA for both types of IL-8 receptors (CXCR1 and CXCR2) was demonstrated by PCR and of both proteins by flow cytometry. Binding and competition studies with 125I-labeled IL-8 and its homologue melanoma growth stimulating activity (125I-labeled MGSA) revealed two specific binding sites for IL-8, K1 = 1.1 x 10(11) M(-1) and K2 = 5 x 10(7) M(-1); and for MGSA, K1 = 2.8 x 10(10) M(-1) and K2 = 5 x 10(7) M(-1). This finding was supported by a dose-dependent rise of cytosolic free calcium concentration ([Ca2+]i) induced by both chemokines and to a lesser extent by the homologue neutrophil-activating peptide-2 (NAP-2). A significant migratory response of human leukemic mast cells (HMC-1) was observed with all three chemokines at a range from 10(-8) M to 10(-9) M. Moreover, the formation of cellular F-actin was induced in a rapid, dose-dependent fashion, with a maximally 1.7-fold increase at 10(-7) M. Using postembedding immunoelectron microscopy, we could show the expression of CXCRI on the cytoplasmatic membrane of isolated human skin mast cells whereas CXCR2 was located in mast cell-specific granules. These findings demonstrate for the first time the functional expression of both types of IL-8 receptors on human mast cells, suggesting a role for their ligands during mast cell activation and recruitment.

Actins↗
PubMed1998

Recombinant adeno-associated virus for the generation of autologous, gene-modified tumor vaccines: evidence for a high transduction efficiency into primary epithelial cancer cells.

To explore the potential of recombinant vectors based on recombinant adeno-associated virus (rAAV) for cancer vaccination, we investigated the transduction efficiency of rAAV into cancer cells ex vivo. Infection of human epithelial cancer cell lines with rAAV carrying reporter genes encoding beta-galactosidase (rAAV/LacZ) or luciferase (rAAV/Luc) resulted in high levels of reporter gene expression (>90% positive cells). In marked contrast, rAAV poorly transduced all murine tumor cell lines, as well as human hematopoietic cell lines. Either irradiation or adenovirus infection of tumor cells prior to rAAV infection induced a 10- to 100-fold increase of reporter gene expression. To determine the transduction efficiency of rAAV into primary cancer cells, freshly isolated, irradiated tumor cells from malignant melanoma and ovarian carcinoma patients were infected with rAAV/Luc, resulting in up to 6.9-fold higher levels of gene expression than in a HeLa tumor cell line. Time course experiments with freshly isolated tumor cells infected with rAAV/Luc showed maximal levels of luciferase expression between days 3 and 9 posttransduction. Simultaneous infection of primary tumor cells with up to three rAAV vectors containing genes encoding the immunostimulatory proteins B7-2 (CD86), p35 subunit of IL-12, and p40 subunit of IL-12 resulted in high expression of B7-2 in more than 90% of the tumor cells and in the secretion of high levels of IL-12. Taken together, our results demonstrate that rAAV efficiently transduces freshly isolated human, epithelial tumor cells and might therefore be a potent tool to produce improved, gene-modified cancer vaccines.

Antigens, CD↗
PubMed1998

CD44 variant isoform expression in a variety of skin-associated autoimmune diseases.

CD44 variant isoforms are frequently expressed on tissue-infiltrating lymphocytes. By the high incidence of autoimmune reactions of the skin and aiming at new strategies of therapeutic intervention, we became interested in evaluating the CD44 isoform expression profile in autoimmune reactions of the skin. Expression of CD44s, CD44v3, v5, v6, v7, v7-v8, and v10 was evaluated in 55 biopsies of lupus erythematosus, bullous pemphigoid, vasculitis, morphea, and pemphigus vulgaris. Biopsies did not contain CD44v5-, CD44v6-, CD44v7-, or CD44v7-v8-positive leukocytes. Staining with anti-CD44v10 was seen in vasculitis and occasionally in lupus erythematosus, morphea, and bullous pemphigoid. All biopsies contained CD44v3(+) leukocytes, the percentage of CD44v3(+) leukocytes being increased in autoimmune infiltrates with the exception of pemphigus vulgaris. CD44v3 was expressed by CD4(+) cells as well as by part of CD8(+) cells, Langerhans cells, and monocytes. Vascular endothelium also contained CD44v3(+) cells. Only monocytes expressed CD44v10. We assume that CD44v3 and CD44v10 may be targeting leukocytes toward the skin or allow for their retention and expansion via binding of cytokines and chemokines harbored by activated, skin-associated endothelium or provided by cells surrounding the infiltrate. The absence of CD44v6, frequently associated with lymphocyte activation, appears to be a peculiarity of skin-infiltrating leukocytes.

Autoimmune Diseases↗
PubMed1998

Vaccination with IL-7 gene-modified autologous melanoma cells can enhance the anti-melanoma lytic activity in peripheral blood of patients with a good clinical performance status: a clinical phase I study.

Recently, cytokine gene transfer into tumour cells has been shown to mediate tumour regression in animal models via immunomodulation. Consequently, a number of clinical protocols have been developed to treat cancer patients with cytokine gene-modified tumour cells. Here, we report the results of a clinical phase I trial using for the first time autologous, interleukin 7 gene-modified tumour cells for vaccination of ten patients with disseminated malignant melanoma. Melanoma cells were expanded in vitro from surgically removed metastases, transduced by a ballistic gene transfer technique and were then injected after in vitro irradiation s.c. at weekly intervals. Clinically, there was no major toxicity except for mild fever, and no major clinical response towards vaccination was observed. Eight of ten patients completed the initial three s.c. vaccinations and were eligible for immunological evaluation. Post vaccination, peripheral mononuclear cells (PBMCs) were found to contain an increased number of tumour-reactive proliferative as well as cytolytic cells, as determined by a limiting dilution analysis. In three of six patients, the frequencies of anti-melanoma cytolytic precursor cells increased between 2.6- and 28-fold. Two of these patients showed a minor clinical response. Analysis of the autologous tumour cell vaccines regarding IL-7 secretion after gene transfer, HLA class I and class II cell surface expression, secretion of immunosuppressive mediators (TGF-beta1, IL-10) and various melanoma-associated tumour antigens revealed a very diverse expression profile. In conclusion, vaccination using gene-modified autologous melanoma cells induced immunological changes in a group of advanced, terminally ill patients. These changes can be interpreted as an increased anti-tumour immune response. However, immunological modulation was most pronounced in patients in good physical condition. Therefore, patients with minimal tumour load or minimal residual disease might preferentially benefit from tumour cell vaccination in further studies. In order to evaluate the effects of the cytokine gene-modified tumour cell vaccines more precisely, an antigenically better defined vaccine is needed.

Adult↗
PubMed1998

Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells.

Melanoma is the main cause of death in patients with skin cancer. Cytotoxic T lymphocytes (CTLs) attack melanoma cells in an HLA-restricted and tumor antigen-specific manner. Several melanoma-associated tumor antigens have been identified. These antigens are suitable candidates for a vaccination therapy of melanoma. Dendritic cells (DCs) are antigen-presenting cells (APCs) specialized for the induction of a primary T-cell response. Mouse studies have demonstrated the potent capacity of DCs to induce antitumor immunity. In the present clinical pilot study, DCs were generated in the presence of granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 4 (IL-4) and were pulsed with tumor lysate or a cocktail of peptides known to be recognized by CTLs, depending on the patient's HLA haplotype. Keyhole limpet hemocyanin (KLH) was added as a CD4 helper antigen and immunological tracer molecule. Sixteen patients with advanced melanoma were immunized on an outpatient basis. Vaccination was well tolerated. No physical sign of autoimmunity was detected in any of the patients. DC vaccination induced delayed-type hypersensitivity (DTH) reactivity toward KLH in all patients, as well as a positive DTH reaction to peptide-pulsed DCs in 11 patients. Recruitment of peptide-specific CTLs to the DTH challenge site was also demonstrated. Therefore, antigen-specific immunity was induced during DC vaccination. Objective responses were evident in 5 out of 16 evaluated patients (two complete responses, three partial responses) with regression of metastases in various organs (skin, soft tissue, lung, pancreas) and one additional minor response. These data indicate that vaccination with autologous DCs generated from peripheral blood is a safe and promising approach in the treatment of metastatic melanoma. Further studies are necessary to demonstrate clinical effectiveness and impact on the survival of melanoma patients.

Adult↗
PubMed1998

Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical results and a first clinical phase I study.

Cytokine gene transfer into tumor cells has been shown to mediate tumor regression and antimetastatic effects in several animal models via immunomodulation. Therefore, clinical protocols have been developed to treat cancer patients with cytokine gene-modified tumor cells. We inserted the genes coding for the p35 and p40 chain of interleukin-12 (IL-12) in two independent eukaryotic expression vectors and transduced melanoma cells of 15 different primary tumor cultures with both plasmids by a ballistic gene transfer approach. Secreted IL-12 demonstrated strong bioactivity by inducing interferon-gamma release from peripheral blood lymphocytes upon coculture with cell culture supernatants after IL-12 gene transfer which could at least partly be blocked by IL-12-specific antisera. Further enrichment of transduced tumor cells by magnetic separation directly after gene transfer increased cytokine secretion from a mean of 119 pg in the unsorted to 507 pg IL-12 (24 h/10(8) cells) in the magnetically enriched cell fraction. Irradiation of these cells led to a further elevation of secreted IL-12 (mean 987 pg). Elevated IL-12 levels were detected over 7 days after irradiation in vitro. In a subsequent first clinical phase I study six patients with metastatic melanoma were vaccinated with autologous, interleukin-12 gene-modified tumor cells. Melanoma cells were expanded in vitro from surgically removed metastases, transduced by ballistic gene transfer, irradiated and were then injected subcutaneously (s.c.) at weekly intervals. Clinically, there was no major toxicity except for mild fever. All patients completed more than four s.c. vaccinations over 6 weeks and were eligible for immunological evaluation. Post-vaccination, peripheral mononuclear cells were found to contain an increased number of tumor-reactive proliferative as well as cytolytic cells as determined by a limiting dilution analysis in two patients. Two patients developed DTH reactivity against autologous melanoma cells and one had a minor clinical response. Biopsies taken from that patient's metastases revealed a heavy infiltration of CD4+ and CD8+ T lymphocytes. In conclusion, vaccination induced immunological changes even in a group of advanced, terminally ill patients. These changes can be interpreted as an increased antitumor immune response.

Adult↗
PubMed1998

Combined treatment of stage IV melanoma patients with amifostine and fotemustine--a pilot study.

Amifostine (Ethyol) is a new chemoprotective agent that has been shown to have significant activity in the prevention of nephro-, oto-, neuro- and haemotoxicity. In preclinical models as well as in clinical trials carried out in patients suffering from various malignancies, the adverse effects and signs of toxicity related to a number of cytostatic drugs, including cisplatin, cyclophosphamide, carboplatin and mitomycin C, were prevented. In Europe fotemustine (Muphoran) is widely used in the treatment of brain metastases in melanoma patients. However, the dose is often limited by severe bone marrow toxicity after induction cycles, particularly in heavily pretreated patients. In order to test whether amifostine treatment might promote bone marrow protective effects when combined with fotemustine chemotherapy, we conducted a preliminary study in 10 patients suffering from stage IV disseminated malignant melanoma. The patients received amifostine (740 mg/m2) prior to fotemustine chemotherapy (100 mg/m2). Six of the patients had failed one or two other prior chemotherapy regimens. Seven patients had brain metastases. Among the 10 patients treated with amifostine and fotemustine, no major clinical responses (complete response or partial response) were achieved, with four patients showing stabilization of the disease over more than 3 months. No patient in the amifostine plus fotemustine treatment group showed severe myelosuppression (WHO grade III/IV), in contrast to a historical control group treated with fotemustine alone, in which about 40% developed major thrombocytopenia and about 45% developed severe leucopenia (WHO grade III/IV). Therefore, we conclude that the combination of amifostine with fotemustine was well tolerated in this small series of patients and further studies are warranted to test the amelioration of myelosuppression by the addition of amifostine.

Amifostine↗
PubMed1998

Differential endothelial adhesion molecule expression in early and late whealing reactions.

In order to clarify the pathomechanisms of fleeting versus more persistent wheals, expression of endothelial adhesion molecules was studied in biopsies of lesional and uninvolved skin of 15 patients with different types of whealing reactions, using immunohistochemistry. In wheals of < or = 30 min duration, no increase of ELAM-1 and ICAM-1 was noted. GMP-140 expression was absent in prick tests, but could be demonstrated in lesions of cholinergic and cold urticaria, with a gradual increase of the latter with time. In wheals of > or = 6 h duration, GMP-140 was only weakly expressed whereas ELAM-1 and ICAM-1 were markedly up-regulated in lesional and less so in nonlesional skin of acute, chronic recurrent and delayed pressure urticaria. This differential expression of endothelial adhesion molecules may reflect the activity of mast cell-derived and other mediators during the elicitation phase and explains the persistence of wheals in different types of urticaria.

Allergens↗
PubMed1997

Enhanced P-selectin expression in chronic and dermographic urticaria.

In both chronic and dermographic urticaria, superficial perivascular leukocytic infiltrations are seen histologically in lesional skin. We have therefore investigated the role of endothelial adhesion molecule expression in these diseases. E-selectin, P-selectin, ICAM-1 and VCAM-1 expression was examined immunohistologically, and the serum levels of the soluble forms of these adhesion molecules were determined by EIA in patients with chronic urticaria, dermographic urticaria as well as in healthy controls (n = 8 in each group) and subjects with symptomatic allergic rhinitis (n = 7) for comparison. A significant increase (p<0.01) was observed for soluble P-selectin in dermographic urticaria (mean 487+/-44 ng/ml) and chronic urticaria (mean 464+/-74 ng/ml) compared to healthy controls (mean 149+/-15 ng/ml) and rhinitis subjects (mean 177+/-30 ng/ml). In contrast, the other adhesion molecules were not significantly elevated in both urticaria groups. Immunohistologically, a strong expression of P-selectin was found in superficial vessels of lesional and nonlesional skin in dermographic urticaria with only a mild increase of the other adhesion molecules studied, supporting the findings observed with the soluble forms in the patients' sera. Since an alteration of soluble P-selectin was not seen in symptomatic allergic rhinitis, an unspecific effect due to inflammation appears to be unlikely. These results therefore point to a potentially relevant role of the endothelial P-selectin expression in the evolution of urticarial whealing.

Case-Control Studies↗
PubMed1997

Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group.

PURPOSE: The combination of interferon alfa-2a (IFN alpha) and high-dose interleukin-2 (IL-2) is active in metastatic melanoma. The addition of cisplatin (CDDP) has resulted in response rates greater than 50%. This study was performed to determine whether the addition of CDDP to a cytokine treatment regimen with IFN alpha and high-dose IL-2 influences survival of patients with metastatic melanoma. PATIENTS AND METHODS: Patients with advanced metastatic melanoma were randomly assigned to receive treatment with IFN alpha 10 x 10(6) U/m2 subcutaneously on days 1 through 5 and a high-dose intravenous decrescendo regimen of IL-2 on days 3 through 8 (18 mIU/ m2/6 hours, 18 mIU/m2/12 hours, 18 mIU/m2/24 hours, and 4.5 mIU/m2/24 hours x 3) without (arm A) or with (arm B) CDDP 100 mg/m2 on day 1. Treatment cycles were repeated every 28 days to a maximum of four cycles. RESULTS: One hundred thirty-eight patients with advanced metastatic melanoma, of whom 87% had visceral metastases, were accrued for the trial. Both regimens were feasible in a multicenter setting. The objective response rate was 18% without and 33% with CDDP (P = .04). The progression-free survival was 53 days without and 92 days with CDDP (P = .02, Wilcoxon; P = .09, log-rank). There was no statistically significant difference in survival between treatment arms, with a median overall survival duration for all patients of 9 months. CONCLUSION: The addition of CDDP to cytokine treatment with IFN alpha and IL-2 does not influence survival of patients with advanced metastatic melanoma, despite a significant increase in response rate and progression-free survival.

Antineoplastic Agents↗