GEIS-21: a multicentric phase II study of intensive chemotherapy including gemcitabine and docetaxel for the treatment of Ewing sarcoma of children and adults: a report from the Spanish sarcoma group (GEIS).

BACKGROUND: First Spanish trial of Ewing sarcoma (ES) including adults and children with the aim to test the efficacy of Gemcitabine and Docetaxel (G/D) in newly diagnosed high-risk (HR) patients. METHODS: This was a prospective, multicentric, non-randomised, open study for patients ⩽40 years with newly diagnosed ES. HR patients (metastatic, axial-pelvic primaries or bone marrow micrometastasis) received 2 window cycles of G/D. Patients with an objective response (OR) to G/D received 12 monthly cycles of G/D after completion of mP6. The primary end point was the OR rate to the G/D window phase and the event-free survival (EFS) and overall survival (OS) for all patients. The study is registered at ClinicalTrials.gov (identifier: NCT00006734). RESULTS: Forty-three patients were enroled, median age 17 years (range, 3-40). After a median follow-up of 43.4 months, the 5-year OS rate is 55.0% (95% CI, 41-74%) with an EFS of 50.0% (95% CI, 36-68%). The 5-year OS and EFS rates for standard risk (SR) patients was 76.0% (95% CI, 57-100%) and 71.0% (CI, 54-94%); for HR 36.0% (CI, 20-65%) and 29.0% (CI, 15-56%). Twelve of 17 (70.6%) high-risk (HR) patients showed an OR (7 PR and 5 SD) to G/D window therapy. The 5-year OS rate for patients ⩽18 years of age was 74.0% (CI, 56-97%) and 31.0% for >18 years (95% CI, 15-66%), P<0.001. Grade 4 adverse events during mP6 occurred in 28/39 of patients (72%) and did not correlate with age. Multivariate survival analyses with <18 vs ⩾18 and risk groups significant differences, P<0.00001. Using a Cox model for OS, both age and risk group were statistically significant (P=0.0011 and P=0.0065, respectively). CONCLUSIONS: Age at diagnosis is an independent prognostic factor superior to the presence of metastases with 18 years as the strongest cut-off. The mP6 regimen provided survival curves that plateau at 3 years and G/D produced significant responses in HR-ES that is worth further exploring.

Gemcitabine plus sirolimus for relapsed and progressing osteosarcoma patients after standard chemotherapy: a multicenter, single-arm phase II trial of Spanish Group for Research on Sarcoma (GEIS).

BACKGROUND: Patients with relapsed unresectable osteosarcoma represents an unmet need, so active and safe systemic treatments are required. Fas cell surface death receptor and mammalian target of rapamycin pathways are implicated in progressing osteosarcoma, and we had preclinical and clinical experience with a scheme that targets both pathways. Therefore, we designed a phase II trial with gemcitabine plus rapamycin, to determine the efficacy and safety, in this subset of patients. PATIENTS AND METHODS: A multicenter, single-arm phase II trial was sponsored by the Spanish Group for Research on Sarcoma. Osteosarcoma patients, relapsed or progressing after standard chemotherapy and unsuitable for metastasectomy received gemcitabine and rapamycin p.o. 5 mg/day except for the same day of gemcitabine administration, and the day before. The main end point was 4-month progression-free survival rate (PFSR), with the assumption that rates higher than 40% would be considered as an active regimen. Translational research aimed to correlate biomarkers with the clinical outcome. RESULTS: Thirty-five patients were enrolled and received at least one cycle. PFSR at 4 months was 44%, and after central radiologic assessment, 2 partial responses and 14 stabilizations (48.5%) were reported from 33 assessable patients. The most frequent grade 3-4 adverse events were: neutropenia (37%), thrombocytopenia (20%), anemia (23%), and fatigue (15%); however, only three patients had febrile neutropenia. Positive protein expression of RRM1 significantly correlated with worse PFS and overall survival, while positivity of P-ERK1/2 was correlated with significant better overall survival. CONCLUSION: Gemcitabine plus sirolimus exhibits satisfactory antitumor activity and safety in this osteosarcoma population, exceeding the prespecified 40% of 4-month PFSR. The significant correlation of biomarkers with clinical outcome encourages further prospective investigation.

A randomized phase III trial comparing induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as treatment of unresectable head and neck cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with unresectable, nonmetastatic locoregionally advanced squamous-cell carcinoma of the head and neck (LASCCHN). This randomized, open-label, phase III clinical trial compared the efficacy between standard CCRT and two different induction chemotherapy (ICT) regimens followed by CCRT. PATIENTS AND METHODS: Patients with untreated LASCCHN were randomly assigned to ICT (three cycles), with either docetaxel (Taxotere), cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CCRT [7 weeks of radiotherapy (RT) with cisplatin 100 mg/m(2) on days 1, 22 and 43]; or 7 weeks of CCRT alone. The primary end points were progression-free survival (PFS) and time-to-treatment failure (TTF). RESULTS: In the intention-to-treat (ITT) population (n = 439), the median PFS times were 14.6 (95% CI, 11.6-20.4), 14.3 (95% CI, 11.8-19.3) and 13.8 months (95% CI, 11.0-17.5) at TPF-CCRT, PF-CCRT and CCRT arms, respectively (log-rank P = 0.56). The median TTF were 7.9 (95% CI, 5.9-11.8), 7.9 (95% CI, 6.5-11.8) and 8.2 months (95% CI, 6.7-12.6) for TPF-CCRT, PF-CCRT and CCRT alone, respectively (log-rank P = 0.90). There were no statistically significant differences for overall survival (OS). Toxic effects from ICT-CCRT were manageable. CONCLUSION: Overall, this trial failed to show any advantage of ICT-CCRT over CCRT alone in patients with unresectable LASCCHN.

Survival Differences of Patients with Resected Extraskeletal Osteosarcoma Receiving Two Different (Neo)Adjuvant Chemotherapy Regimens: A Systematic Review and Meta-analysis.

AIMS: Extraskeletal osteosarcoma (ESOS) is a malignant tumour developing in soft tissues, characterised by the production of osteoid or bone matrix by tumour cells. The standard treatment for localised ESOS is wide resection. Radiotherapy and chemotherapy are usually incorporated into the management of patients. Two types of chemotherapy regimen are mostly used: an osteosarcoma-type chemotherapy, based on cisplatin, and a soft-tissue sarcoma (STS)-type chemotherapy, using the combination of doxorubicin and ifosfamide. To investigate the difference in survival between these two chemotherapy regimens, a systematic review of studies reporting the 5-year disease-free survival (DFS) rates among patients with ESOS submitted to surgery and who received (neo)adjuvant chemotherapy with osteosarcoma-type or STS-type chemotherapy was carried out. MATERIALS AND METHODS: Of the 401 articles identified by systematically searching the PubMed, Embase and Cochrane Central Register of Controlled Trials databases, six retrospective studies were included in the final analysis. In total, 319 patients with localised/resected ESOS were included in the study. RESULTS: Our meta-analysis showed a benefit in 5-year DFS favouring the use of osteosarcoma-type chemotherapy (relative risk = 1.32, 95% confidence interval 1.03-1.69; P = 0.54); I2 heterogeneity was 0%. The 5-year DFS rate was 56.3% (95% confidence interval 48.3-64.3) with osteosarcoma-type chemotherapy and 45.2% (95% confidence interval 34.5-55.9) with STS-type chemotherapy, with I2 heterogeneity of 27% and 0%, respectively. CONCLUSIONS: Our analysis suggests that there may be a difference regarding the type of (neo)adjuvant chemotherapy regimen used in the treatment of patients with resected ESOS in favour of osteosarcoma-type chemotherapy. Future studies evaluating the role of this treatment modality in this scenario need to consider the type of chemotherapy regimen when comparing with an arm of surgery with/without radiotherapy alone.

Efficacy of immune checkpoint inhibitors in alveolar soft-part sarcoma: results from a retrospective worldwide registry.

BACKGROUND: Conventional cytotoxic drugs are not effective in alveolar soft-part sarcoma (ASPS). Immune checkpoint (programmed cell death protein 1/programmed death-ligand 1) inhibitors (ICIs) are promising drugs in ASPS. A worldwide registry explored the efficacy of ICI in ASPS. MATERIALS AND METHODS: Data from adult patients diagnosed with ASPS and treated with ICI for advanced disease in expert sarcoma centers from Europe, Australia and North America were retrospectively collected, including demographics and data related to treatments and outcome. RESULTS: Seventy-six ASPS patients, with a median age at diagnosis of 25 years (range 3-61 years), were registered. All patients received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 38 patients (50%) and combination in 38 (50%) (23 with a tyrosine kinase inhibitor). Among the 68 assessable patients, there were 3 complete responses and 34 partial responses, translating into an overall response rate of 54.4%. After a median follow-up of 36 months [95% confidence interval (CI) 32-40 months] since the start of immunotherapy, 45 (59%) patients have progressed on ICI, with a median progression-free survival (PFS) of 16.3 months (95% CI 8-25 months). Receiving ICI in first line (P = 0.042) and achieving an objective response (P = 0.043) correlated with a better PFS. Median estimated overall survival (OS) from ICI initiation has not been reached. The 12-month and 24-month OS rates were 94% and 81%, respectively. CONCLUSIONS: This registry constitutes the largest available series of ASPS treated with ICI. Our results suggest that the ICI treatment provides long-lasting disease control and prolonged OS in patients with advanced ASPS, an ultra-rare entity with limited active therapeutic options.

SEOM clinical guidelines for the treatment of head and neck cancer (2020).

Head and neck cancers (HNC) are defined as malignant tumours located in the upper aerodigestive tract and represents 5% of oncologic cases in adults in Spain. More than 90% of these tumours have squamous histology. In an effort to incorporate evidence obtained since 2017 publication, the Spanish Society of Medical Oncology (SEOM) presents an update of the squamous cell HNC diagnosis and treatment guideline. Most relevant diagnostic and therapeutic changes from the last guideline have been updated: introduction of sentinel node biopsy in early oral/oropharyngeal cancer treated with surgery, concomitant radiotherapy with weekly cisplatin 40 mg/m2 in the adjuvant setting, new approaches for HPV-related oropharyngeal cancer and new treatments with immune-checkpoint inhibitors in recurrent/metastatic disease.

Long-term outcomes of induction chemotherapy followed by chemoradiotherapy vs chemoradiotherapy alone as treatment of unresectable head and neck cancer: follow-up of the Spanish Head and Neck Cancer Group (TTCC) 2503 Trial.

BACKGROUND: Our previous phase-3 study (TTCC 2503) failed to show overall survival advantage of 2 induction chemotherapy (IC) regimens followed by standard concurrent chemoradiotherapy (CRT) over CRT alone in patients with unresectable locally advanced head and neck squamous-cell carcinoma (LAHNSCC). This study described the long-term survival of those patients. MATERIALS AND METHODS: Long-term follow-up study of patients with untreated LAHNSCC assigned to IC (three cycles), with either docetaxel, cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CRT, or CRT alone, included in the previous TTCC 2503 trial. RESULTS: In the intention-to-treat population (n = 439), the median OS times were 25.4 (95% CI, 16.8-34.4), 26.2 (95% CI, 18.2-36.6) and 25.4 months (95% CI, 17.4-36.0) in the TPF-CRT, PF-CRT and CRT arms, respectively (log-rank p = 0.51). In the per-protocol population (n = 355), patients with larynx-hypopharynx primary tumors treated with IC (TPF or PF) followed by CRT had a longer median PFS than those who received CRT alone. Moreover, patients with ECOG 0 treated with IC (TPF or PF) followed by CRT had a better TTF than those with CRT alone. There were no statistically significant differences in terms of OS, PFS or TTF, according to the tumor load or affected nodes. CONCLUSION: After a long follow-up, the TTCC 2503 trial failed to show the benefit of IC-CRT in unresectable LAHNSCC regarding the primary end point. However, fit patients with ECOG 0 and primary larynx-hypopharyngeal tumors may benefit from the use of IC if administered by an experienced team. ClinicalTrials.gov identifier NCT00261703.

Sequential chemotherapy regimen of induction with panitumumab and paclitaxel followed by radiotherapy and panitumumab in patients with locally advanced head and neck cancer unfit for platinum derivatives. The phase II, PANTERA/TTCC-2010-06 study.

BACKGROUND: Sequential treatment of Panitumumab (Pb) plus Paclitaxel (Px) as induction treatment (IT) followed by concurrent bioradiotherapy (Bio-RT) with Pb may be an alternative for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) in patients ineligible for high-dose cisplatin therapy. METHODS: Phase II, single-arm, multicentre study, with two-stage design, in patients ≥ 18 years with stage III-IVa-b LA-SCCHN unfit for platinum. Patients received Px + Pb (9 weeks) as IT followed by Bio-RT + Pb. Primary endpoint: overall response rate (ORR) after IT, defined as: more than 70% of patients achieving complete response (CR) or partial response (PR) to IT. Secondary end-points: progression-free survival, organ preservation rate, safety profile. RESULTS: Study ended prematurely (51 patients) due to slow recruitment. ORR: 66.7% (95% CI: 53.7-79.6), 8 (15.7%) CR and 26 (51.0%) PR. 39 patients (76%) completed radiotherapy (RT). Pb and/or Px-related adverse events (AEs) grade 3-4: 56.9% during IT and 63.4% during the concomitant phase, of which most common were skin toxicity (33.3%). Five deaths occurred during treatment, two of them (3.9%) were Pb and/or Px-related. CONCLUSIONS: Although underpowered, ORR was higher than the pre-specified boundary for considering the treatment active. Although Px + Pb as IT provides some benefit, the safety profile is worse than expected. To consider Pb + Px as IT as an alternative for platinum-unsuitable LA-SCCHN, further research/investigation would be needed.

Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment.

BACKGROUND: Platinum-based therapy (PBT) is the standard therapy for recurrent and/or metastatic head and neck cancer (HNC), but the incidence of recurrence remains high. This study evaluates the efficacy and tolerability of capecitabine as palliative monotherapy for recurrent HNC previously treated with PBT. METHODS: Patients aged 18-75 years, with Eastern Cooperative Oncology Group performance status 0-2, squamous HNC with locoregional and/or metastatic recurrence previously treated with PBT and adequate organ functions, were included. Capecitabine (1.250 mg m(-2) BID) was administered on days 1-14 every 21 days for at least two cycles. RESULTS: A total of 40 male patients with a median age of 58 years were analysed. All patients received a median number of four cycles of capecitabine (range: 1-9) and the median relative dose intensity was 91%. Seven patients were not evaluable for response. Overall response rate was 24.2%. Median time to progression and overall survival were 4.8 and 7.3 months, respectively. Haematological adverse events (AEs) grade 3/4 were reported in six patients. Most common grade 3/4 non-haematological AEs were asthenia (12.5%), palmar-plantar eritrodisestesia (10%), mucositis (10%), dysphagia (10%) and diarrhoea (7.5%). CONCLUSIONS: Capecitabine seems to be an active, feasible and well-tolerated mode of palliative treatment for advanced HNC patients who have previously received PBT schedules.

Prognostic time dependence of deletions affecting codons 557 and/or 558 of KIT gene for relapse-free survival (RFS) in localized GIST: a Spanish Group for Sarcoma Research (GEIS) Study.

BACKGROUND: To assess whether deletions involving codons 557 and/or 558 (critical deletions) of exon 11 of KIT are relevant in the prognosis of relapse-free survival (RFS) in gastrointestinal stromal tumor (GIST) patients with a long follow-up. PATIENTS AND METHODS: A univariate and multivariate analysis for RFS were carried out on 162 localized GIST patients over the entire follow-up period and over the intervals 0-4 years and >4 years. Factors assessed among others were Fletcher/National Institutes of Health and Miettinen-Lasota/Armed Forces Institute of Pathology (M-L/AFIP) risk categories, critical deletions and non-deletion-type mutation (NDTM) within exon 11 of KIT. RESULTS: Multivariate analyses revealed that M-L/AFIP [relative risk (RR) 11.45, confidence interval (CI) 4.40-29.76, for the high-risk subgroup and RR 5.97, CI 2.09-17.06, for the intermediate subgroup] and critical deletions (RR 3.05, CI 1.59-5.85) were independent prognostic factors for RFS for the first 4 years and for the entire follow-up period. Beyond 4 years, the high-risk M-L/AFIP subgroup (RR 8.12, CI 1.48-44.4) and NDTM (RR 6.42, CI 1.17-35.12) were independent prognostic factors for RFS. The median follow-up was 84 months. CONCLUSION: Critical deletions represent a time-dependent prognostic factor limited to the first 4 years after surgery, which could help identify a subset with higher and earlier risk for relapse in GIST patients.

SEOM clinical guideline in nasopharynx cancer (2017).

Nasopharyngeal carcinoma (NPC) is distinct from other cancers of the head and neck in biology, epidemiology, histology, natural history, and response to treatment. Radiation therapy is an essential component of curative-intent of non-disseminated disease and the association of chemotherapy improves the rates of survival. In the case of metastatic disease stages, treatment requires platinum/gemcitabine-based chemotherapy and patients may achieve a long survival time.

Multidisciplinary management of head and neck cancer: First expert consensus using Delphi methodology from the Spanish Society for Head and Neck Cancer (part 1).

Head and neck cancer is one of the most frequent malignances worldwide. Despite the site-specific multimodality therapy, up to half of the patients will develop recurrence. Treatment selection based on a multidisciplinary tumor board represents the cornerstone of head and neck cancer, as it is essential for achieving the best results, not only in terms of outcome, but also in terms of organ-function preservation and quality of life. Evidence-based international and national clinical practice guidelines for head and neck cancer not always provide answers in terms of decision-making that specialists must deal with in their daily practice. This is the first Expert Consensus on the Multidisciplinary Approach for Head and Neck Squamous Cell Carcinoma (HNSCC) elaborated by the Spanish Society for Head and Neck Cancer and based on a Delphi methodology. It offers several specific recommendations based on the available evidence and the expertise of our specialists to facilitate decision-making of all health-care specialists involved.

Epidemiological characteristics of a Spanish cohort of patients diagnosed with squamous cell carcinoma of head and neck: distribution of risk factors by tumor location.

PURPOSE: Head and neck cancer is a highly heterogeneous disease comprising a large number of tumors located in the cervicofacial area. This study aimed to determine the epidemiological characteristics of squamous-cell carcinomas of the head and neck in the Spanish population, and the distribution of risk factors based on tumor locations. METHODS/PATIENTS: A cohort of 459 patients (75 oral cavity, 167 oro-/hypopharyngeal and 217 laryngeal cancers) recruited in 19 hospitals participating in the Spanish head and neck cancer cooperative group were included over 3 years (2012-2014). Epidemiological parameters and risk factors were obtained from a self-administered questionnaire, and tumor characteristics were obtained from clinical records. Multivariate multinomial logistic regression was used to assess factors associated with tumor location. RESULTS: Most patients were males (88.4 %), smokers (95 %) and drinkers (76.5 %). Relative to laryngeal cancer, pharyngeal cancer and oral cancer were more common in women than men (OR 3.58, p = 0.003 and 4.33, p = 0.001, respectively); pharyngeal cancer was more associated with rural environment (OR 1.81, p = 0.007) and weekly alcohol intake (10-140 g: OR 2.53, p = 0.012; 141-280 g: OR 2.47, p = 0.023; >280 g: OR 3.20, p = 0.001) and less associated with pack-years of smoking (21-40 packs: OR 0.46, p = 0.045; 41-70 packs: OR 0.43, p = 0.023; ≥71 packs: OR 3.20, p = 0.015). CONCLUSIONS: The distribution of these tumors differs between the sexes, with a higher proportion of oral cavity and pharyngeal tumors in women than in men. Oro-/hypopharyngeal cancers were more strongly associated with rural areas and with alcohol consumption, although less strongly associated with smoking than laryngeal tumors.

SEOM Clinical Guideline of management of soft-tissue sarcoma (2016).

Soft-tissue sarcomas are uncommon and heterogeneous tumors of mesenchymal origin. A soft-tissue mass that is increasing in size, greater than 5 cm, or located under deep fascia are criteria for suspicion of sarcoma. Diagnosis, treatment, and management should preferably be performed by a multidisciplinary team in reference centers. MRI and lung CT scan are mandatory for local and distant assessment. A biopsy indicating histological type and grade is needed previous to the treatment. Wide surgical resection with tumor-free tissue margin is the primary treatment for localized disease. Radiotherapy is indicated in large, deep, high-grade tumors, or after marginal resection not likely of being improved with reexcision. Neoadjuvant and adjuvant chemotherapy improve survival in selected cases, usually in high-grade sarcomas of the extremities. In the case of metastatic disease, patients with exclusive lung metastasis could be considered for surgery. First-line treatment with anthracyclines (or in combination with ifosfamide) is the treatment of choice. New drugs have shown activity in second-line therapy and in specific histological subtypes.

Phase I trial of weekly irinotecan combined with UFT as second-line treatment for advanced colorectal cancer.

The aim of this study was to determine the maximum-tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly Irinotecan (CPT-11) plus UFT, and to assess the antitumour activity of this combination as second-line chemotherapy in patients with advanced colorectal carcinoma, 31 patients with measurable advanced colorectal carcinoma were treated. Cohorts of 3 patients received increasing dose levels of the combination. Levels 1 to 4 included a fixed dose of oral (p.o.) UFT (250 mg/m(2)/day) for 21 days of a 28-day cycle combined with increasing intravenous (i.v.) doses of CPT-11 (80, 100, 110 and 120 mg/m(2)) on days 1, 8 and 15. Levels 5 and 6 included a higher fixed dose of oral UFT (300 mg/m(2)) combined with increasing i.v. doses of CPT-11 (100 and 110 mg/m(2)) on days 1, 8 and 15. 147 courses were administered. MTD were reached at level 4 (2 cases of grade 4 diarrhoea and 1 grade 3 asthenia), and level 6 (1 grade 4 diarrhoea, 1 grade 3 diarrhoea and 1 grade 3 febrile neutropenia). Responses in 30 evaluable patients were: 3 partial responses (10%), 15 stable disease (50%) and progressive disease in 12 patients (40%). Median time to progression was 4.5 months (95% Confidence Interval (CI): 3.4-6.6 months) and median survival was 11 months (95% CI: 7.9-14.1 months). The recommended doses for phase II trials are: (a) CPT-11 110 mg/m(2) i.v. on days 1, 8 and 15 every 28 days plus UFT 250 mg/m(2) p.o. on days 1 through to 21 or (b) CPT-11 100 mg/m(2) and UFT 300 mg/m(2).

Prognostic impact of bulky mediastinal lymph nodes (N2>2.5 cm) in patients with locally advanced non-small-cell lung cancer (LA-NSCLC) treated with platinum-based induction chemotherapy.

A group of 70 patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treated in different phase II-III trials with platinum-based chemotherapy in two institutions, have been evaluated to identify potential baseline prognostic factors predicting their survival. The eligibility criteria were patients with stage IIIA (N2)-IIIB, Eastern Cooperative Oncology Group performance status 0.1 and less than 5% weight loss. All 37 patients with stage IIIA(N2) were treated with platinum-based induction chemotherapy followed by surgery plus radiotherapy if no progression was observed. The other 33 patients with stage IIIB were treated with platinum-based induction chemotherapy followed by conventional fractionation radiotherapy if no progression was observed. The overall response rate to induction chemotherapy was 40%. Median survival of the 70 patients was 13 months, with a 4-year survival of 15%. At univariate analysis, two prognostic factors correlated with survival: partial or complete response to induction chemotherapy (P<0.00001) and bulky mediastinal lymph nodes (N2>2.5 cm) (P=0.03). At multivariate analysis, only the response to induction chemotherapy retained statistical significance (P=0.00001). Randomized well-balanced prospective trials considering initially mediastinal N2 node size are needed to clearly establish the role of chemotherapy, surgery and radiotherapy in LA-NSCLC.

[Parenteral nutrition in oncologic patients]. / Nutrición parenteral en pacientes oncológicos.

The aim of this work is to carry out a follow-up of oncological inpatients who received parenteral nutrition (PN). We analysed the connection between the clinical situations and the indication and type of PN administered. A retrospective review of oncological patients who received PN during 1996 was carried out. Age, sex, primary tumor, PN indication and compliance degree, nutritional evolution, different categories of nutritional intervention, characteristics of PN as well as related complications and connected with PN were analysed. 33 patients, 23 female and 10 male, between 20 and 82 years old, were studied. 39% received PN with intensive antineoplastic therapy; 55% received PN as supportive treatment in various clinical situations related to the tumor or with antineoplastic therapy; 6% received palliative PN. 25 patients received PN without lipids and 8 total PN. The mean duration of PN was 10 days. 17 patients received PN by peripheric venous route and 16 through central venous catheter. The PN was well tolerated. In conclusion, most patients (94%) complied with some of the criteria established for the PN indication. The biggest percentage of patients in treatment with PN were divided into two main groups: patients with intensive antineoplastic therapy and patients with gastrointestinal disfunction caused by tumor or antineoplastic therapy. The role of PN in oncological patients it is not defined yet. The incidence of complications due to PN was low and without clinical relevance.

Value of FDG-PET for monitoring treatment response in patients with advanced GIST refractory to high-dose imatinib. A multicenter GEIS study.

AIM: The aim of this study was to evaluate the utility of positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) in monitoring response in refractory GIST. METHODS: This multicenter study prospectively evaluated 21 patients with locally advanced and/or metastatic GIST refractory to with high-dose imatinib (800 mg/day) treated with doxorubicin 15-20 mg/m2/weekly for 4 cycles, followed by imatinib maintenance (400 mg/day). CT and FDG-PET were performed at baseline and after completion of therapy. RESULTS: Mean baseline tumor size on CT was 5.9 cm. Median progression-free survival (PFS) was 219 days (range 62-1108). Three out of 21 patients (14%) had partial responses (PR) under RECIST criteria, 12 patients (57%) remained stable (SD) and 6 showed progression (PD) of the disease during treatment (29%). Six patients had PR by FDG-PET, 15 showed SD (n=9) or PD (n=6) based on EORTC criteria. Patients with a PFS <6 mo showed a significantly higher ∑SUVmax at baseline (26.04±13.4) than those with PFS≥6 mo (9.82±5.0) (P<0.05). A correlation was found between PET response and PFS: PR 14±6.1 mo, SD 5.5±0.8 mo and PD 3.5±4.1 mo (P<0.05). A residual SUVmax <5 after treatment correlated with improved PFS (314±315 days vs 131±91 days) (P<0.01). Survival curves showed a significant association between PET response and PFS (P<0.05). Patients with wild-type genotype KIT (KIT-WT) showed a significantly lower baseline SUVmax (5.36±1.4) than non-WT KIT (8.40±3.6) (P<0.05). CONCLUSION: FDG-PET is useful in assessing response of GIST refractory to imatinib and correlates with the presence of KIT-WT. Baseline ∑SUVmax can predict response to treatment in this series.

Phase I/II trial of doxorubicin and fixed dose-rate infusion gemcitabine in advanced soft tissue sarcomas: a GEIS study.

The aim of the study was to determine the dose-limiting toxicity and maximum tolerated dose of a first-line combination of doxorubicin and gemcitabine in adult patients with advanced soft tissue sarcomas and to explore its activity and toxicity, and the presence of possible interactions between these agents. Patients with measurable disease were initially treated with doxorubicin 60 mg m(-2) by i.v. bolus on day 1 followed by gemcitabine at 800 mg m(-2) over 80 min on days 1 and 8, every 21 days. Concentrations of gemcitabine and 2',2'-difluorodeoxyuridine in plasma, and gemcitabine triphosphate levels in peripheral blood mononuclear cells were determined during 8 h after the start of gemcitabine infusion. Myelosuppression and stomatitis were limiting toxicities, and the initial dose level was applied for the Phase II trial, where grade 3-4 granulocytopenia occurred in 70% of patients, grade 3 stomatitis in 46% and febrile neutropenia in 20%. Objective activity in 36 patients was 22% (95% CI: 9-35%), and a 50% remission rate was noted in leiomyosarcomas. Administration of doxorubicin preceding gemcitabine significantly reduced the synthesis of gemcitabine triphosphate. Clinical activity, similar to that of single-agent doxorubicin, and the toxicity encountered do not justify further studies with this schedule of administration.