A cross-sectional, comparative, syndromic description of oncological mixed pain in Medical Oncology units in Spain.

OBJECTIVE: The reason cancer pain remains prevalent and hard to classify may be partially explained by the failure to identify neuropathic mechanisms. The objective of this research was to identify the syndromes of cancer pain that may be particularly hard to manage due to their mixed pathophysiology. DESIGN: A series of 384 patients who had cancer of any type, at any stage, and suffered from chronic pain (symptom onset > 3 months) were assessed during a routine return visit in Spain. Medical oncologists indicated the presence and pathophysiology of 33 predefined pain syndromes on a per-patient basis. This information was then measured against clinical, psychosocial, and health care-related data to determine which syndromes pose particular challenges. RESULTS: The mean (standard deviation) age of patients was 61.6 (12.6) years, 49.7% were women. Most (82%) had advanced metastatic disease, 68.7% were on second-line or palliative therapies. The worst syndrome was nociceptive, pure neuropathic, and mixed in 34.6, 26.9, and 38.6% of patients, respectively. Any syndrome could be of mixed pathophysiology. Only 10 syndromes were common (≥ 5% of patients). Syndromes related to malignant bone pain and involvement of chest wall structures were the most frequent. Certain syndromes (including tumor-related bone pain, chemotherapy-induced peripheral neuropathies, paraneoplastic pain syndromes, and malignant neuralgias or injury to cranial nerves) can be particularly challenging when they have a mixed pathophysiology, because the neuropathic component is rarely or unevenly considered. CONCLUSIONS: Virtually all cancer pain syndromes can present mixed pathophysiology. Certain syndromes can include neuropathic components that are frequently overlooked.

Colorectal cancer molecular classification using BRAF, KRAS, microsatellite instability and CIMP status: Prognostic implications and response to chemotherapy.

OBJECTIVE: The aim of this study was to validate a molecular classification of colorectal cancer (CRC) based on microsatellite instability (MSI), CpG island methylator phenotype (CIMP) status, BRAF, and KRAS and investigate each subtype's response to chemotherapy. DESIGN: This retrospective observational study included a population-based cohort of 878 CRC patients. We classified tumours into five different subtypes based on BRAF and KRAS mutation, CIMP status, and MSI. Patients with advanced stage II (T4N0M0) and stage III tumours received 5-fluoruracil (5-FU)-based chemotherapy or no adjuvant treatment based on clinical criteria. The main outcome was disease-free survival (DFS). RESULTS: Patients with the combination of microsatellite stable (MSS) tumours, BRAF mutation and CIMP positive exhibited the worst prognosis in univariate (log rank P<0.0001) and multivariate analyses (hazard ratio 1.75, 95% CI 1.05-2.93, P = 0.03) after adjusting for age, sex, chemotherapy, and TNM stage. Treatment with 5-FU-based regimens improved prognosis in patients with the combination of MSS tumours, KRAS mutation and CIMP negative (log rank P = 0.003) as well as in patients with MSS tumours plus BRAF and KRAS wild-type and CIMP negative (log-rank P<0.001). After adjusting for age, sex, and TNM stage in the multivariate analysis, only patients with the latter molecular combination had independently improved prognosis after adjuvant chemotherapy (hazard ratio 2.06, 95% CI 1.24-3.44, P = 0.005). CONCLUSION: We confirmed the prognostic value of stratifying CRC according to molecular subtypes using MSI, CIMP status, and somatic KRAS and BRAF mutation. Patients with traditional chromosomally unstable tumours obtained the best benefit from adjuvant 5-FU-based chemotherapy.

Analysis of clinical prognostic factors for survival and time to progression in patients with metastatic colorectal cancer treated with 5-fluorouracil-based chemotherapy.

Colorectal cancer (CRC) is one of the most common malignant tumors in adults. Twenty-five percent of patients are not amenable to surgical resection because they have locally advanced or metastatic disease. For these patients, median survival time is between 4 and 13 months, and chemotherapy is used mainly with palliative intent. We conducted this study to evaluate potential prognostic factors for time to progression and survival. A retrospective review of 91 patients with metastatic CRC treated with bolus 5-fluorouracil-based chemotherapy (Mayo Clinic schedule) was performed. Univariate and multivariate analyses of clinical prognostic factors were carried out. Median follow-up time was 53 months (range, 17-107 months). Median time to disease progression was 9.6 months, and median survival time was 15.4 months. Actuarial 5-year survival was 17%. In the univariate analyses, factors predictive of time to progression were visceral metastases, elevated alkaline phosphatase (AP) levels, performance status (PS), and elevated carcinoembryonic antigen (CEA) and CA 19-9 levels. Multivariate analyses confirmed the independent prognostic value of PS and AP levels. In the univariate analyses for survival, significant prognostic factors were visceral metastases, hypoalbuminemia, elevated lactate dehydrogenase levels, elevated AP levels, PS, and elevated CEA and CA 19-9 levels. In the multivariate analyses, only PS, elevated CEA and CA 19-9 levels, and liver involvement retained prognostic significance. This study confirms the prognostic value of PS for both time to progression and survival. AP levels are significantly related to time to progression. Additional factors influencing survival time are elevated tumor marker levels and the existence of liver metastases.

Phase II trial of induction irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for unresectable, locally advanced gastric and oesophageal-gastric junction adenocarcinoma.

PURPOSE: The prognosis of patients with unresectable M0 gastric cancer remains very poor. We performed a phase II trial to explore the efficacy and toxicity of induction irinotecan-cisplatin (IC) followed by concurrent irinotecan-cisplatin and radiotherapy (IC/RT) in this setting. METHODS AND MATERIALS: Patients with unresectable M0 gastric (GC) or oesophageal-gastric junction (EGJC) adenocarcinomas were treated with two courses of IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on days 1 and 8 every 21 days) followed by IC/RT (daily radiotherapy-45 Gy-with concurrent IC: irinotecan, 65 mg/m(2), and cisplatin, 30 mg/m(2), on days 1, 8, 15, and 22). Resectability was reassessed after this treatment, and surgical resection was performed if feasible. The primary endpoint was the R0 resection rate after induction treatment. RESULTS: Seventeen patients were included in the study (EGJC: 6; GC: 11). An R0 resection was achieved in only 5 patients (29%), and according to the design of the trial (Simon's optimal two-stage) accrual of patients was terminated after the first stage. No patient died during IC, whereas 3 patients (24%) died during IC/RT and one of 5 resected patients (20%) died during the first 30 days after resection. The median survival was 10.5 months, and the actuarial 2-year survival rate was 27%. CONCLUSIONS: Induction IC followed by IC/RT showed poor efficacy and significant toxicity in patients with unresectable GC/EGJC.

Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma.

PURPOSE: To determine in a Phase II trial whether preoperative irinotecan-cisplatin (IC) followed by concurrent IC therapy and radiotherapy (IC/RT) improved outcome in patients with resectable, locally advanced gastric adenocarcinoma (GC) or esophagogastric junction cancer (EGJC). PATIENTS AND METHODS: Patients with resectable Stage II-IV, M0 GC or EGJC made up the study population. The primary endpoint was pathologic complete response (pCR). Two courses of IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on Days 1 and 8 every 21 days) were given. Patients without progression then received IC/RT, consisting of daily radiotherapy (45Gy) with concurrent IC (irinotecan, 65 mg/m(2); cisplatin, 30 mg/m(2) on Days 1, 8, 15, and 22). Surgical resection was performed, if feasible, 5-8 weeks after the end of radiotherapy. RESULTS: Twenty-three patients were included in the study: 10 with EGJC and 13 with GC. Two patients (9%) achieved pCR. The incidences of Grade 3-4 toxicities were as follows: IC: neutropenia 35% (febrile 13%), anemia 22%, diarrhea 22%, emesis 8%; IC/RT: neutropenia 52% (febrile 5%), asthenia 19%, anemia 9%, emesis 9%, diarrhea 5%, cardiotoxicity 5%. No patients died during IC or IC/RT. R0 resection was achieved in 15 patients (65%). Median survival was 14.5 months, and the actuarial 2-year survival rate was 35%. CONCLUSIONS: Preoperative IC followed by IC/RT resulted in moderate response and resection rates with mild toxicity in patients with GC and EGJC.

Colorectal cancer metastasis resectability after treatment with the combination of oxaliplatin, irinotecan and 5-fluorouracil. Final results of a phase II study.

PURPOSE: To investigate the response rate of the triple combination of oxaliplatin (L-OHP) in combination with irinotecan (CPT-11) and 5-fluorouracil (5-FU) and to assess its impact on secondary resectability of previously non-resectable liver metastasis (LM). PATIENTS AND METHODS: Patients > or = 18 with MCRC, ECOG grade 0-2, and no prior treatment received L-OHP (85 mg/m(2)), CPT-11 (150 mg/m(2)) and 5-FU (2 250 mg/m(2) in 48 h CI) on D1 every 15 days. RESULTS: Forty-seven patients with initially non-resectable metastatic disease were included. Median age 62 years (38-76); 28 males; 26 patients with 0 performance status (ECOG) 40 patients had prior surgery and four adjuvant chemotherapy. All patients were evaluable for toxicity and 42 for response. Main grade 3-4 toxicities were neutropenia (40%), febrile neutropenia (4%), diarrhea (21%), nausea/vomiting (11%/15%), fatigue (11%), anemia and alopecia (9% each); grade 3-4 neurotoxicity was observed in 28% patients. Secondary surgery was possible in 15 of 47 (31.9%) patients and 12/30 (40%) patients with only LM: in this cohort, median OS has not been reached at 22 months median follow-up, with 2/12 patients having died. Overall response rate was 69% (95% CI, 53-82%); 13 (31%) had stable disease. Median time to progression and overall survival (OS) were 10.9 (95% CI, 9.9-13.2) and 19.9 (95% CI, 11.7-TBD) months, respectively. CONCLUSION: This combination has shown promising activity with manageable toxicity as front-line treatment in MCRC, and has allowed the resectability of LM in a considerable number of patients, offering them the possibility of long-term survival.

[Amyopathic dermatomyositis associated with a recurrence of breast cancer]. / Dermatomiositis amiopática asociada a recurrencia de cáncer de mama.

The term "amyopathic dermatomyositis", or dermatomyositis "sine myositis" is used to describe those patients who present with the skin manifestations typical of dermatomyositis, but with no evidence of inflammatory myopathy. Amyopathic dermatomyositis may be associated with an underlying neoplasm, the same as with classic dermatomyositis. We present the case of a 59-year-old female patient, with cutaneous findings typical of dermatomyositis, with no proximal muscle weakness and with normal serum muscle enzymes, which stayed in a normal range throughout the later follow-up period, although the electromyogram performed six months later showed alterations with a myopathic pattern. These skin symptoms raised the suspicion of an occult neoplasm, and a recurrence of the patient's breast cancer, apparently inactive for many years, was finally found. The association of amyopathic dermatomyositis with a recurrence of breast cancer is exceptional.

Toxic epidermal necrolysis associated with interleukin-2.

BACKGROUND: Metastatic renal cell carcinoma (MRCC) has been characteristically unresponsive to chemotherapy. In lieu of an effective regimen, interleukin-2 (IL-2) and interferon alfa are considered drugs of choice to treat this cancer. Subcutaneous IL-2 is safe and well tolerated, with a mortality rate <3%. OBJECTIVE: To report a case of cutaneous and hematologic toxicity in a patient treated with IL-2. CASE SUMMARY: A 67-year-old woman received radiotherapy and immunotherapy for cancer that had metastasized to the bone and lungs. IL-2 was part of the regimen. After 5 days of treatment with IL-2, the patient developed a hemorrhagic lesion that progressed to toxic epidermal necrolysis, as well as grade 4 pancytopenia. She died 10 days after treatment was begun. At the time of death, leukocytes were 0.3 x 10(3)/mm(3), platelets 10 x 10(3)/mm(3), and hemoglobin 6.8 mg/dL. DISCUSSION: Cutaneous IL-2 adverse effects are frequent, but generally mild and reversible. The adverse hematologic effects are usually transitory and pancytopenia is not frequent. The severity of cutaneous and hematologic toxicity experienced by our patient has rarely been reported. CONCLUSIONS: The use of IL-2 in bedridden patients with performance status >2 must be given on an individualized basis. If radiotherapy over extensive areas of the body is needed, the use of IL-2 must be postponed until radiotherapy is completed.

Phase I study of the combination of oxaliplatin, irinotecan and continuous infusion 5-fluorouracil in digestive tumors.

Oxaliplatin (L-OHP), irinotecan (CPT-11) and 5-fluorouracil (5-FU) have shown their efficacy in metastatic colorectal cancer. The synergism of these drugs has been demonstrated in vivo and in vitro. The aim of this study was to determine the recommended dose of the triple combination of L-OHP, CPT-11 and CI 5-FU for a further phase II study. Eighteen patients received the study treatment in four dose levels. The male:female ratio was 15:3 and the median age was 51.6 years (range 30-71). The type of tumor was colon in eight patients, rectum in four and other locations in six patients. The treatment was repeated every 2 weeks, at the fixed dose of L-OHP, 85 mg/m, and escalated doses of CPT-11 and 48-h infusion 5-FU of 100/2000, 100/2250, 125/2250 and 150/2250 mg/m. Only one previous treatment for the advanced disease was permitted. Patients received a median of 8 cycles (range 1-26) and a total of 152 cycles were administered. Dose intensity administered at dose level L-OHP 85 mg/m, CPT-11 150 mg/m and 5-FU 2250 mg/m was 95, 92 and 95% for L-OHP, CPT-11 and 5-FU, respectively. One patient in level 2 and one patient in level 4 presented dose-limiting toxicity that was not confirmed in the three required additional patients by level. The anti-tumor activity was assessed in nine patients: seven partial responses, one stable disease and one progressive disease. The maximum-tolerated dose was not reached, and thus the recommended dose for this combination schedule is L-OHP, 85 mg/m, CPT-11, 150 mg/m and 5-FU, 2250 mg/m 48-h continuous infusion, the same doses that were recommended for the drugs when administered in combination therapy of L-OHP + 5-FU or CPT-11 + 5-FU. A phase II study in first-line treatment of patients with metastatic colorectal cancer with this dose regimen is ongoing.

Multicenter phase I study of irinotecan plus raltitrexed in patients with 5-fluorouracil-refractory advanced colorectal cancer.

Irinotecan and raltitrexed are active against advanced colorectal cancer, act through different mechanisms, and have non-overlapping toxicity profiles. In vitro studies have shown a schedule-dependent synergism between both drugs. The aim of this multicenter study was to determine the maximum tolerated dose (MTD) of this combination. Patients with 5-fluorouracil-refractory, advanced colorectal cancer were eligible. Dose escalation consisted of irinotecan (250-350 mg/m(2) as a 60-min infusion) in combination with a fixed dose of raltitrexed (3 mg/m(2) as a 15-min infusion, 1 h after irinotecan). Courses were repeated every 21 days. Three to 6 patients were to be included at each dose level. Dose limiting (NCI-CTC grade 3-4) toxicities (DLT) were assessed during the first 2 cycles. Thirteen patients were recruited (4, 3 and 6 in levels I, II and III, respectively). Main toxicity was diarrhea and asthenia, whereas myelotoxicity was mild. At level III, 2/6 patients experienced DLT (grade 4 diarrhea and neutropenia). The MTD was not reached, but further dose escalation was not attempted. Among 12 patients with measurable disease, 2 partial responses were observed for an overall response rate of 17%. The combination of single-agent full doses of irinotecan (350 mg/m(2)) and raltitrexed (3 mg/m(2)) in a 3-weekly schedule is feasible, with mild toxicity and a promising clinical activity. Diarrhea is the DLT, but it is not more common or severe than that described with irinotecan alone.

Papel de la ventriculografía isotópica en el seguimiento de pacientes oncológicos sometidos a tratamiento con antraciclinas / Paper of the ventriculography in patients treated with anthracyclines

Objetivo: El objetivo de este trabajo es calcular la fracción de eyección (FE) mediante ventriculografía isotópica en los pacientes tratados con antraciclinas, intentando analizar la dosis de adriamicina que condiciona la cardiotoxicidad. Material y método: Se realizó una revisión retrospectiva de las historias clínicas de 28 pacientes procedentes del Servicio de Oncología, a los que se les había practicado más de una ventriculografía isotópica, la segunda tras tratamiento con antraciclinas. Estudiamos 12 mujeres y 16 varones de edades comprendidas entre 16 y 72 años (media 43, mediana 45 años) con diferentes diagnósticos oncológicos siendo los más frecuentes: Sarcomas (39 por ciento); Carcinoma de mama (22 por ciento) y Linfoma no-Hodgkin (22 por ciento). Calculamos para cada paciente la dosis total de antraciclinas recibidas (adriamicina y 4-epirrubicina) incluyendo también las antraciclinas recibidas antes del primer estudio isotópico (cardiotoxicidad acumulada). Debido a que la 4-epirrubicina es menos cardiotóxica que la adriamicina se convierten las cifras de 4-epirubicina a adriamicina (siguiendo la relación: 50mg/m2 de adriamicina se corresponden con 75mg/m2 de 4-epirrubicina). Se compararon las medias previas y tras tratamiento de las FE de ambos ventrículos y se calculó si existían diferencias mediante el test de la t de Student para datos apareados. Resultados: La t de Student de las medias de las FE del Ventrículo izquierdo (V.I.) antes y tras el tratamiento fue 4.08 (existen diferencias estadísticamente significativas para una p<0.01) sin embargo para el ventrículo derecho la t fue 1.79 lo que indica que no existieron diferencias estadísticamente significativas (p=0.09)...

Venlafaxina retard y trastorno por dependencia de alcohol / Venlafaxine extended release and alcohol dependence

Objetivos: Determinar el efecto del tratamiento con venlafaxina retard en pacientes con trastorno por dependencia de alcohol o de alcohol y cocaína que inician un tratamiento de desintoxicación. Metodología: Estudio observacional, abierto y prospectivo, realizado en España en 2005. Se incluyen 55 pacientes mayores de 18 años con diagnóstico de trastorno por dependencia de alcohol o alcohol y cocaína, ingresados en un centro de Atención Especializada para iniciar tratamiento de desintoxicación. Se administró durante 6 meses venlafaxina retard, a dosis entre 75 y 225 mg/día. Resultados: El tratamiento se asoció a reducciones significativas en las puntuaciones del EuropASI en las siguientes áreas: 3, uso de alcohol, con una puntuación basal y final de 8,2 ± 0,2 y 6,4 ± 0,4, respectivamente (P < 0,01); 5, relaciones familiares/sociales, puntuación inicial de 6,9 ± 0,2 y final de 5,2 ± 0,5 (P < 0,001); 1, situación médica, con puntuaciones de 3,7 ± 0,4 y 0,9 ± 0,3 (visitas basal y final, respectivamente) (P < 0,001); y 6, situación psiquiátrica, con puntuación basal de 7,8 ± 0,1 y final de 5,4 ± 0,4 (P < 0,001). La puntuación basal en la Escala Visual Analógica de craving de alcohol fue de 26,7 ± 4,6, descendiendo a 4,1 ± 1,5 en la visita final (P < 0,001). Conclusiones: Los resultados de este estudio observacional sugieren que venlafaxina retard podría ser efectiva en el tratamiento coadyuvante de pacientes dependientes de alcohol, que están siguiendo terapia de deshabituación. No obstante, esto debe ser replicado con series más amplias y controladas con placebo

Objectives: The aim is to determine the effect of the treatment with venlafaxine extended release in patients with alcohol or cocaine dependence disorder that initiate detoxification treatment. Methods: Observational, open, prospective study carried out in Spain in 2005. 55 patients older than 18 years of age with diagnosis of alcohol and/or cocaine dependence disorder, hospitalized in Specialty Care Center to initiate detoxification treatment, were included. Daily doses of 75 to 225 mg of venlafaxine extended release were administered for 6 months. Results: Treatment was associated with significant reductions in EuropASI scores in the following areas: 3, alcohol use, baseline and final score of 8.2±0.2 and 6.4±0.4, respectively (P < 0.01); 5, family/social relations, initial score of 6.9±0.2 and of 5.2±0.5 at endpoint (P < 0.001); 1, medical status, scores of 3.7±0.4 and 0.9±0.3 (baseline and final visits, respectively) (P < 0.001); and 6, psychiatric status, with a baseline score of 7.8±0.1 and final score of 5.4±0.4 (P < 0.001). The VAS alcohol craving scores at baseline were 26.7±4.6, decreasing to 4.1±1.5 at endpoint (P < 0.001). Conclusions: The results of this observational study suggest that venlafaxine extended release could be effective as a coadyuvant in the treatment of alcohol dependent patients in alcohol detoxification therapy. Nevertheless, this should be confirmed with bigger placebo-controlled samples

Dermatomiositis amiopática asociada a recurrencia de cáncer de mama / Amyopathic dermatomyositis associated with a recurrence of breast cancer

El término dermatomiositis amiopática, o dermatomiositis sine miositis designa aquellos pacientes que presentan las manifestaciones cutáneas típicas de la dermatomiositis pero sin evidencia de miopatía inflamatoria. La dermatomiositis amiopática puede asociarse a neoplasia subyacente, al igual que sucede con la dermatomiositis clásica. Se presenta el caso de una paciente de 59 años, con hallazgos cutáneos característicos de dermatomiositis, sin debilidad muscular proximal y con enzimas musculares séricas normales, que se mantuvieron en el rango de la normalidad a lo largo del seguimiento posterior, aunque el electromiograma realizado 6 meses más tarde mostró alteraciones con patrón miopático. Esta sintomatología cutánea permitió sospechar una neoplasia oculta y finalmente encontrar una recidiva de su cáncer de mama aparentemente inactivo desde hacía muchos años. La asociación de dermatomiositis amiopática con recurrencia de cáncer de mama es excepcional

The term «amyopathic dermatomyositis», or dermatomyositis «sine myositis» is used to describe those patients who present with the skin manifestations typical of dermatomyositis, but with no evidence of inflammatory myopathy. Amyopathic dermatomyositis may be associated with an underlying neoplasm, the same as with classic dermatomyositis. We present the case of a 59-year-old female patient, with cutaneous findings typical of dermatomyositis, with no proximal muscle weakness and with normal serum muscle enzymes, which stayed in a normal range throughout the later follow-up period, although the electromyogram performed six months later showed alterations with a myopathic pattern. These skin symptoms raised the suspicion of an occult neoplasm, and a recurrence of the patient's breast cancer, apparently inactive for many years, was finally found. The association of amyopathic dermatomyositis with a recurrence of breast cancer is exceptional