Clinical impact of preoperative tumour contact with superior mesenteric-portal vein in patients with resectable pancreatic head cancer.

INTRODUCTION: The NCCN classification of resectability in pancreatic head cancer does not consider preoperative radiological tumour ≤ 180° contact with portal vein/superior mesenteric vein (PV/SMV) as a negative prognostic feature. The aim of this study is to evaluate whether this factor is associated with higher rate of incomplete resection and poorer survival. METHODS: All patients considered for pancreatic resection between 2012 and 2017 at two Spanish referral centres were included. Patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC) according to NCCN classification were excluded. Preoperative CT scans were reviewed by dedicated radiologists to identify radiologic tumour contact with PV/SMV. RESULTS: Out of 302, 71 patients were finally included in this study. Twenty-two (31%) patients showed tumour-PV/SMV contact (group 1) and 49 (69%) did not show any contact (group 2). Patients in group 1 showed a statistically significantly higher rate of R1 and R1-direct margins compared with group 2 (95 vs 28% and 77 vs 10%) and lower median survival (24 vs 41 months, p = 0.02). Preoperative contact with PV/SMV, lymph node metastases, R1-direct margin and NO adjuvant chemotherapy were significantly associated with disease-specific survival at multivariate analysis. CONCLUSION: Preoperative radiological tumour contact with PV/SMV in patients with NCCN resectable PDAC is associated with high rate of pathologic positive margins following surgery and poorer survival.

Prognostic role of the histological subtype of melanoma on the hands and feet in Caucasians.

Acral melanoma (AM) is associated with a poor prognosis in part because of delayed diagnosis, but probably also because of other intrinsic characteristics of location. The aim of this study was to review the specific characteristics and outcome of AM in Caucasians. This was a cross-sectional retrospective clinical-pathological study of 274 patients identified with AM in the database of a referral unit in Europe from 1986 to 2010. The mean age of the patients was 56.6 (SD 17.7) years. 269 cases could be histologically classified and included in the study. In all, 222 (82.5%) were located on feet. According to melanoma subtype, 165 (61.3%) were acral lentiginous melanoma (ALM), 84 (31.2%) were superficial spreading melanoma (SSM), and 20 (7.5%) were nodular melanoma (NM). SSM patients were characterized by female predominance (77.4%), younger age, and classic melanoma-risk phenotype (fair skin and multiple nevi). Among the 198 invasive cases with a mean follow-up of 56.2 months, the mean (SD) Breslow's thickness was 3.1 (3.6) mm, being 1.4 (1.4) mm in SSM, 3.5 (4.1) mm in ALM and 4.9 (2.9) mm in NM (P<0.001). Ulceration was present in 33.3%, 2.9% in SSM, 38.6% in ALM, and 76.9% in NM (P<0.001). A total of 29.3% relapsed (7.3% of SSM, 35% of ALM and 55% of NM) and 24.2% died because of AM. In multivariate analysis, age at diagnosis, Breslow, and histopathological subtype were independent prognostic factors for both disease-free and AM-specific survival. The ALM and NM subtypes presented poorer outcome after weighting Breslow and age (P=0.02). Histological subtype of AM could have an impact on biological behavior, ALM and NM subtypes presenting a poorer prognosis after adjusting for age and Breslow's thickness.

Spanish Multidisciplinary Melanoma Group (GEM) guidelines for the management of patients with advanced melanoma.

Advanced melanoma is a relatively uncommon condition whose therapeutic management has undergone major changes over the past four years. The present article aims to establish recommendations for the management of these patients based on the best available evidence reached by consensus of a group of professionals familiar in the treatment of these patients. These professionals, belonging to Spanish Multidisciplinary Melanoma Group, reviewed the diagnostic process and the incorporation of new techniques of molecular diagnosis of advanced disease; treatment and monitoring of stage III both as adjuvant locoregional treatments have been addressed, as well as new therapies for stage IV. We have reviewed the palliative treatment alternatives for disseminated disease, such as surgery, radiotherapy or non-cytotoxic systemic treatments. Finally, we have also reviewed the most relevant toxicities of new drugs and their management in clinical practice.

A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study.

PURPOSE: Sorafenib, an oral inhibitor of B-raf, VEGFR2, and PDGFR2-beta, acts against pancreatic cancer in preclinical models. Due to the radio-sensitization activity of both sorafenib and gemcitabine, we designed a multicenter, phase I trial to evaluate the safety profile and the recommended dose of this combination used with concomitant radiation therapy. METHODS: Patients with biopsy-proven, unresectable pancreatic adenocarcinoma (based on vascular invasion detected by computed tomography) were treated with gemcitabine (300 mg/m2 i.v. weekly ×5 weeks) concurrently with radiation therapy (45 Gy in 25 fractions) and sorafenib (escalated doses in a 3+3 design, from 200 to 800 mg/day). Radiation portals included the primary tumor but not the regional lymph nodes. Patients with planning target volumes (PTV) over 500 cc were excluded. Cases not progressing during chemoradiation were allowed to continue with sorafenib until disease progression. RESULTS: Twelve patients were included. Three patients received 200 mg/day, 6 received 400 mg/day, and 3 received 800 mg/day; PTVs ranged from 105 to 500 cc. No dose-limiting toxicities occurred. The most common grade 2 toxicities were fatigue, neutropenia, nausea, and raised serum transaminases. Treatment was discontinued in one patient because of a reversible posterior leukoencephalopathy. There were no treatment-related deaths. CONCLUSION: The addition of sorafenib to concurrent gemcitabine and radiation therapy showed a favorable safety profile in unresectable pancreatic adenocarcinoma. A dose of 800 mg/day is recommended for phase II evaluation. TRIAL REGISTRATION: EudraCT 2007-003211-31 ClinicalTrials.gov 00789763.

Whole abdominal radiotherapy in ovarian cancer.

OBJECTIVES: The aim of the study was to evaluate the clinical outcome and toxicity after adjuvant whole abdominal radiotherapy (WART) in patients with ovarian cancer. MATERIAL AND METHODS: Ten patients with optimal cytoreduced ovarian cancer, with a mean age of 58 years (40-70) and stage Ic: 4, stage II: 2, stage III: 4, were treated with WART and adjuvant chemotherapy (9/10). The total radiation dose was 22.5 Gy in the whole abdomen and 42-45 Gy in the pelvis. RESULTS: The mean follow-up was 8 years. The 5-year actuarial disease-free survival (DFS) was 60%, and the overall survival (OS) was 70%. Four patients had disease recurrence. The sites of recurrence were the abdomen in 2 patients and distant metastases in the other 2 patients (liver and brain metastasis). Gastrointestinal toxicity was as follows: acute 3/10 grades I and II, and late toxicity: 2/10 grades I and II, and only 1 patient developed small bowel obstruction (SBO) that required surgery. CONCLUSIONS: Whole abdominal radiotherapy after surgery and platinum-based chemotherapy achieves high locoregional disease control with an acceptable risk of acute toxicity.

Loco-regional control after postoperative radiotherapy for patients with regional nodal metastases from melanoma.

INTRODUCTION: The role of adjuvant radiation therapy (RT) following nodal surgery in malignant melanoma remains controversial. There are no published randomised trials comparing surgery alone to surgery with postoperative RT. AIM AND METHODS: The purpose of the present retrospective study was to review the results of loco-regional control after postoperative RT in patients with nodal metastases of melanoma. Seventy-seven patients with high-risk disease (lymph nodes > or =3 cm, more than three lymph nodes involved, extracapsular extension and recurrent disease) were treated with adjuvant RT. Hypofractionation was used in 65 patients and conventional fractionation in 12 patients. RESULTS: Seventy-seven patients with nodal metastases from melanoma were managed with lymphadenectomy and radiation, with or without systemic therapy. The median age was 56 years old (range: 21-83). There were 47 males (61%) and 30 females (39%). Loco-regional control was observed in 95% of patients (73/77). The actuarial 5-year in-field loco-regional control rate was 90% (mean: 105 months; CI95%: 96-115 months). Median metastasis disease- free survival (MDFS) was 16 months (CI95%: 13-18 months). Median survival time (MST) for the entire group was 26 months (CI95%: 18-34 months). MST according to the localisation of node metastases (groin, axilla and cervical) was also analysed, without statistically significant differences (p=0.08). Concerning the number of risk factors score, analysis of survival did not show statistically significant differences (p=0.055). CONCLUSIONS: Despite the high incidence of distant metastases, loco-regional control remains an important goal in the management of melanoma. Surgery and adjuvant RT provides excellent loco-regional control, although distant metastases remain the major cause of mortality.

[Quality of life and survival after surgical treatment of metastatic femoral fractures]. / Calidad de vida y supervivencia tras el tratamiento quirúrgico de las fracturas metastásicas del fémur.

BACKGROUND AND OBJECTIVES: To analyze the results of the surgical treatment of proximal femoral fractures secondary to metastatic bone disease, in terms of quality of life improvement and survival. MATERIAL AND METHOD: A transversal prospective study was carried out during a period of 15 months in which 20 fractures of femur from 19 patients were included, corresponding to 10 imminent fractures (IF) and 10 established fractures. Assessed final outcomes were associated complications, walking type at discharge and change in Karnofsky's scale after surgery. Mortality and survival after operation were also registered. RESULTS: Surgical procedures performed were osteosynthesis (72%) and femoral arthroplasty (28%). With regard to complications, 1 patient died during the intra-operatory period and there was 1 failure of ostesyntesis that required re-operation. There was an improvement in the quality of life measured according to the Karnofsky scale after the surgery (P=.017). Survival after surgery was 2 months in the group of patients with impending fracture and 5 months in the group of patients with established fracture (P=.816). CONCLUSIONS: Patients who underwent surgery for a femoral fracture secondary to a metastatic disease showed an improvement in the quality of life, according to the Karnofsky scale. Although they represent a group of patients with a short survival, the control of pain and functional improvement justifiy the procedure.

Phase I trial of neoadjuvant chemoradiotherapy (CRT) with capecitabine and weekly irinotecan followed by laparoscopic total mesorectal excision (LTME) in rectal cancer patients.

BACKGROUND: To analyze the feasibility of capecitabine with weekly irinotecan and concurrent radiotherapy followed by laparoscopic-total mesorectal excision (LTME) in rectal cancer patients. METHODS: Eligible criteria included adenocarcinoma of the rectum staged by endoscopic ultrasonography (u), spiral abdominal and pelvic CT and chest X-ray. Patients received weekly irinotecan 50 mg/m(2) (days 1, 8, 15, 22, 29) and capecitabine (days 1 through 5 for 5 weeks); dose level; (DL) I 250 mg/m(2)/bid; DL II 375 mg/m(2)/bid; DL III 500 mg/m(2)/bid, according to phase I methodology. External beam radiotherapy was delivered up to a total dose of 45 Gy in daily fractions of 1.8 Gy, 5 days a week. LTME was planned 5-7 weeks after CRT. RESULTS: From February 2003 to February 2006, 22 patients were included. Median age was 62 (range 48 to 78). Seven pts were uT3N0 and 15 pts uT3N1. Seven patients were treated at DL I, six at DL II and nine at DL III. Grade 3 adverse events were observed in all levels. The maximum tolerated dose was reached at 375 mg/m(2) (DL II). Conversion rate to open surgery was 5%. Median hospital stay was 6.6 days. One month post-surgical complications were noted in five patients (23%). Median excised nodes were 11 (range 4-21). Pathological complete response was observed in two patients (9%). CONCLUSIONS: LTME after preoperative CRT with CAPIRI is feasible but severe adverse events were found in all levels despite the use of lower dose of capecitabine than previously published.

Brain nodules with lung mass: are they always metastases?

In a smoking adult with a lung mass, brain masses are usually diagnosed as brain metastases of lung origin. Nevertheless, differential diagnosis between cerebral abscesses cannot be performed based on clinical symptoms or imaging technologies, and histological diagnosis is essential. This case illustrates the advisability of always obtaining histological diagnosis of the primary tumor and/or cerebral lesion before introducing any oncological treatment.

Dihydropyrimidine dehydrogenases and cytidine-deaminase gene polymorphisms as outcome predictors in resected gastric cancer patients treated with fluoropyrimidine adjuvant chemotherapy.

BACKGROUND AND OBJECTIVES: Single nucleotide polymorphisms of dihydropyrimidine dehydrogenases gene (DPYD) induces dihydropyrimidine dehydrogenase enzyme (DPD) deficiency resulting in increased activity of 5-fluorouracil derivatives. Cytidine-deaminase gene (CDA) polymorphisms have been involved in prognosis in experimental tumours. METHODS: Analysis of 50 consecutive resected gastric cancer patients who received adjuvant chemotherapy with Tegafur for polymorphisms of genes DPYD1 (A/G; Ile543Val), DPYD2 (C/T; Arg29Cys) and CDA (A/C; Lys27Gin). The status of alleles (wild-type or at least one polymorphism) was correlated with outcome and toxicity. RESULTS: Polymorphisms frequencies wild-type/non-wild-type were 36/14 in DPYD1 (A/G; Ile543Val); 26/24 in DPYD2 (C/T; Arg29Cys); and 17/23 in CDA (A/C; Lys27Gin) or between homozygous/heterozygous were 39/11 in DPYD1; 33/17 in DPYD2 and 26/24 in CDA respectively. After 77 months of median follow-up (SD = 26.3), 18 patients died of tumour relapse. Better survival was observed in DPYD1 patients only, for non-wild-type over wild-type (P = 0.0214); and in patients with one or more heterozygous polymorphisms in any of the three genes tested (P = 0.0017). In 10 pts (20%) total dose was reduced by toxicity, only 3 of them were homozygous. CONCLUSIONS: Gene polymorphisms of DPYD and CDA predict survival of gastric cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy.

Diagnostic efficacy of bone scintigraphy, magnetic resonance imaging, and positron emission tomography in bone metastases of myxoid liposarcoma.

Myxoid liposarcomas (MLS) have a tendency to metastasize to unusual sites. We report an unusual case of bone metastases not detected by bone scan and neither by fluorodeoxyglucose positron emission tomography (PET-FDG) and successfully identified with magnetic resonance imaging (MRI) in a patient with metachronic MLS. Histopathological examination of the primary tumor evidenced a tumor with unfavorable prognostic markers, and the biopsy of an iliac bone lesion confirmed the diagnosis of metastatic disease. On histological grounds, the tumor showed features of a more differentiated neoplasm without foci of round cells or necrosis in the latter. MRI allowed the identification of disseminated disease compared to computed tomography (CT) and PET scans. Thus, because of the heterogeneous histological features of MLS and the biological behavior of the disease, a combined approach of FDGPET-CT and MRI, may allow a more accurate staging of soft tissue sarcomas.

Toxicity of combined treatment of adjuvant irradiation and interferon alpha2b in high-risk melanoma patients.

Surgically resected stage III melanoma patients commonly receive adjuvant therapy with interferon (IFN) alpha2b. For those patients with high-risk features of draining node recurrence, radiation therapy can also be considered as a treatment option. The purpose of this retrospective study was to assess the efficacy and radiation-related toxicity of this combined therapy. Eighteen patients receiving adjuvant IFNalpha2b therapy during radiation therapy, or within 1 month of its completion, were reviewed retrospectively and analysed for outcome. Radiation was delivered at 600 cGy dose per fraction, in 16 out of 18 patients, twice a week, and at 200 cGy dose per fraction in two patients five times a week. Total radiation dose and number of fractions were as follows: 30 Gy/5 fr (n=8), 36 Gy/6 fr (n=8) and 50 Gy/25 fr (n=2). The percentage of disease-free patients, with no local recurrence, at 3 years was 88%. In 10 patients, IFNalpha2b was administered concurrently with radiotherapy; in three, within 30 days before or after radiation; and in five, more than 30 days after radiation. All the patients experienced acute skin reactions, grade I on the Radiation Therapy Oncology Group (RTOG) scale. Late radiation-related toxicity was seen in one patient with grade III (RTOG) skin reaction and two with grade IV (RTOG) radiation-induced myelitis. Concurrent use of adjuvant radiotherapy and IFNalpha2b might enhance radiation-induced toxicity, and special care should be taken when the spinal cord is included in the radiation field.

Clinical outcome after surgical resection of lung metastases from melanoma.

BACKGROUND: Surgical therapy plays an important role in the management of selected patients with metastatic melanoma. PURPOSE: A retrospective review of 13 patients who underwent surgical resection of lung metastases from melanoma from 1996 to 2003 was performed. The aim of the study was to analyze the clinical outcome and survival time. MATERIALS AND METHODS: Mean age was 45 years old (range: 31-64). Complete tumour resection was confirmed histologically. Nine patients presented one single pulmonary lesion, two lesions (n = 3) and three lesions (n = 1) but in all cases confined in the same pulmonary lobe. RESULTS: Median survival time (MST) for the entire group was 20 months (95% confidence interval (CI): 16-24 months). The median time to disease progression after lung metastasectomy was 5 months (95% CI: 3-7 months). MST, according to the prognostic groups proposed by the International Registry of Lung Metastases, was 17 months (95% CI: 6-28 months) for group I (n = 6), MST of 20 months (95% CI: 16-24 months) for group II (n = 5) and MST of 4 months for group III (n = 2), without differences statistically significant (log-rank p = 0.423). MST regarding the time of disease free interval from diagnostic of primary tumour and lung metastases (< 36 months [n = 5] vs > 36 months [n = 8]) was 20 months and 17 months respectively, without differences statistically significant (log rank p = 0.222). CONCLUSIONS: Surgical resection when feasible provides survival rates superior to any available nonsurgical therapy. In carefully selected patients, when the resection is performed with curative intent, it may result in improved survival.

Phase I trial of gefitinib with concurrent radiotherapy and fixed 2-h gemcitabine infusion, in locally advanced pancreatic cancer.

PURPOSE: Pancreatic cancers are resistant to radiotherapy (RT) and current chemotherapy agents. Epidermal growth factor receptor is overexpressed in pancreatic cancer, and in vitro studies have shown that epidermal growth factor receptor inhibitors can overcome radio- and chemoresistance. The aim of the study was to determine whether the addition of gefitinib to RT and gemcitabine for patients with locally advanced pancreatic carcinoma (LAPC) was feasible and safe. METHODS AND MATERIALS: Eighteen patients with pathologically proven LAPC, based on major vascular invasion based on helical computed tomography (CT) and endoscopic ultrasound, were entered into the study. The targeted irradiated volume included the tumor and 2-cm margin. Prophylactic irradiation of regional nodes was not allowed. Patients with >500 cm(3) of planning tumor volume were excluded. An initial cohort of 6 patients was treated with RT (45 Gy/25 fractions/5 weeks) plus concomitant gefitinib (250 mg/day). Successive cohorts of patients received 100, 150, and 200 mg/m(2)/day of gemcitabine in a 2-h infusion over Weeks 1, 2, 3, 4, and 5 with gefitinib (250 mg/day) and RT. Gefitinib was continued after RT until progression. A pharmacodynamic study of angiogenic markers was also performed to evaluate a possible antiangiogenic effect. RESULTS: There were no dose-limiting toxicities. Common toxicities were mild neutropenia, asthenia, diarrhea, cutaneous rash and nausea/vomiting. The median (95% confidence interval [CI]) progression-free survival was 3.7 (95% CI = 1.9-5.5) months, and the median overall survival was 7.5 (95% CI = 5.2-9.9) months. No significant reduction of vascular endothelial growth factor and interleukin-8 was observed after treatment. CONCLUSION: Our results support that the combination of gefitinib, RT, and gemcitabine has an acceptable toxicity but with modest activity in LAPC.

Results of radiotherapy in primary cutaneous lymphoma.

INTRODUCTION: Multiple therapeutic strategies have been proposed for the management of primary cutaneous lymphomas. We report the outcome data and therapeutic response of a group of patients treated with local radiotherapy. MATERIAL AND METHODS: Twenty seven patients with diagnostic of cutaneous lymphoma and treated with local radiation were evaluated for clinical response. Thirteen cases corresponded to cutaneous T-cell lymphomas (CTCL) and 14 to cutaneous B-cell lymphomas (CBCL). Orthovoltage radiotherapy of 100 Kv was used and total dose of radiation ranged from 15 to 30 Gy (mean 24 Gy; median 20 Gy). RESULTS: The immediate response to the treatment was satisfactory in all cases. In 24 patients (89%) complete response was obtained in the irradiated lesion and in 3 cases (11%) the response was partial. With a mean follow-up of 25.4 months (range 1-100 months) the overall response rate was 96.3%. Fourteen patients (52%) were alive without evidence of disease (6 CTCL and 8 CBCL), 5 patients (18%) retained cutaneous disease or had systemic progression (3 CTCL and 2 CBCL) and 8 patients died (30%). In 7 patients lymphoma progression was the factor leading to death (26%) and in one patient the cause was not related with the disease. CONCLUSIONS: Radiotherapy was demonstrated to be able to induce clinical remission of primary cutaneous lymphomas.

Whole brain irradiation and temozolomide based chemotherapy in melanoma brain metastases.

INTRODUCTION: Whole brain irradiation (WBRT) remains a recommended treatment for patients with brain metastases from malignant melanoma in terms of symptom palliation, especially when extracranial systemic disease is present. Temozolomide (TMZ) has shown efficacy in the treatment of metastatic melanoma. The objective was to evaluate the potential benefit in survival of two different schedules of total dose and fractionation (20 Gy/5 fractions vs 30 Gy/10 fractions) and further TMZ based chemotherapy. MATERIALS AND METHOD: We have conducted a retrospective study in a group of twenty-one patients (RTOG Recursive Partitioning Analysis class II) of the use of WBRT with 20 Gy/5 fractions (n = 11) and 30 Gy/10 fractions (n = 10). All patients received further TMZ based chemotherapy administered as a single chemotherapeutic agent or in combination with chemo-immunotherapy. RESULTS: Prognostic variables such as: age, Karnofsky performance status, extracranial metastases and number of brain metastases, were analyzed in both groups of treatment without statistically significant differences. The median survival time (MST) for WBRT 20 Gy group was 4 months (CI 95%: range 2- 6 months) and for WBRT 30 Gy group was 4 months (CI 95%: range 0-7 months) without statistically significant differences (Log rank p = 0.74). There was one complete response and two partial responses. CONCLUSIONS: The results suggest that MST was not significantly affected by the total dose/fractionation schedule.

Biochemotherapy with temozolomide, cisplatin, vinblastine, subcutaneous interleukin-2 and interferon-alpha in patients with metastatic melanoma.

The aim of this study was to determine the efficacy and tolerability of a biochemotherapy regimen, including low-dose subcutaneous interleukin-2 and temozolomide, in patients with metastatic melanoma. Treatment consisted of temozolomide (150 mg/m per day on days 1-5), cisplatin (20 mg/m per day intravenously on days 1-4), vinblastine (1.5 mg/m per day on days 1-4), interleukin-2 (4.5 MU/m per day subcutaneously on days 5-8) and interferon-alpha2b (5 MU subcutaneously on days 5-9, 11, 13, 15, every 28 days). Thirty-six patients were included. Patients with poor prognostic factors were not excluded. Seventeen patients (47%) had been treated previously in an adjuvant setting with interferon-alpha. Four patients (11%) had been treated previously with chemotherapy and six (17%) had been treated with other biochemotherapy regimens. The distribution by American Joint Committee on Cancer staging was as follows: M1a in two patients (6%), M1b in 11 patients (31%) and M1c in 23 patients (64%). At inclusion, seven patients (19.4%) had cerebral metastases that had previously been treated with whole brain radiotherapy. For thirty-four evaluable patients, seven (20.5%) achieved an objective response. Overall, metastatic disease was substantially decreased or temporarily stabilized in 11 patients (32.4%; 95% confidence interval, 17.4-50.5). Responses were observed for all locations. The central nervous system was the initial site of relapse in two responding patients. The median survival was 10 months. The main toxicities noted were haematological (grades 3-4): neutropenia (1.8%), thrombocytopenia (1.8%) and anaemia (1.2%). It can be concluded that this regimen is well tolerated and has a modest activity despite the poor prognosis of our patient population. The low haematological toxicity rate obtained suggests that higher doses could be tried.

Biochemotherapy with low doses of subcutaneous interleukin-2 in patients with melanoma: results of a phase II trial.

INTRODUCTION: Metastatic melanoma has an ominous prognosis. Bio-chemotherapy regimens can increase the response rate but with a high degree of toxicity due, mainly, to the use of high-dose intravenous interleukin-2. OBJECTIVES: To test the feasibility and activity profile of a bio-chemotherapy regimen of low-dose subcutaneous interleukin-2. MATERIAL AND METHODS: Administration scheme: dacarbazine at 200 mg/m2/d on days 1-4, cisplatin at 20 mg/m2/d intravenous on days 1-4, vinblastine at 1.5 mg/m2/d on days 1-4, IL-2 at 4.5 MUI/m2/d subcutaneous on days 5-8, IFN-alpha at 5 MU subcutaneous on days 5-9, 11, 13, 15 of every 21-day cycle. RESULTS: Objective response was obtained in 11 patients (39.3%; 95%CI: 21-59) including 4 with complete response (14.3%; 95%CI: 4-33). With an extended follow-up of 49 months and 60 months, respectively, 2 patients continue with complete response. The main toxicities were haematological: grade 3-4 neutropenia in 8.2% of cycles, thrombocytopenia in 1.2% and anaemia in 3.2%. CONCLUSIONS: The regimen is safe and has a good activity profile. The presence of long-term survivors, despite the use of lower doses and subcutaneous IL-2, is encouraging.