Safety and preliminary efficacy of electrostatic precipitation during pressurized intraperitoneal aerosol chemotherapy (PIPAC) for unresectable carcinomatosis.

INTRODUCTION: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) was recently introduced to treat unresectable peritoneal metastases. Adding an electrostatic field may enhance charged droplet precipitation and tissue penetration, resulting in improved anticancer efficacy. We report for the first time its safety and preliminary efficacy. MATERIALS AND METHODS: Patients underwent PIPAC combined with an electrostatic field, using the Ultravision™ apparatus. Adverse events were scored with the Common Terminology Criteria. Treatment response was assessed after more than one PIPAC, using clinical symptoms, tumor markers, CT imaging and histological regression. RESULTS: Forty-eight patients (median age, 61 y) with diverse primary tumors underwent 135 procedures (median per patient, 3). Most (65.2%) were treated as outpatient. Twenty-eight (58.3%) patients received concomitant chemotherapy. The most frequent treatment-related toxicities were anemia (grade 1 to 3, 13 [9.6%]), ileus (grade 1 to 3, 5 [3.7%]), anorexia (grade 1 to 3, 6 [4.4%]), nausea (grade 1 to 3, 5 [3.7%]) and vomiting (grade 1 to 3, 7 [5.2%]). There was no grade 4 or 5 morbidity. Twenty (41.7%) patients did not complete three treatments, mainly because of disease progression (n = 13). After two procedures, there were one responder and 8 non-responders. After three treatments, we observed 11 responders, two patients with stable disease, and 15 non-responders. All but one patient with therapy response received simultaneous chemotherapy. CONCLUSION: Electrostatic precipitation during PIPAC is well tolerated and safe. After three procedures and concomitant chemotherapy, response or stable disease is achieved in approximately half of cases. These findings warrant prospective trials in homogeneous patient cohorts.

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.

Prospective randomised phase II study of docetaxel versus paclitaxel administered weekly in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy.

BACKGROUND: Docetaxel and paclitaxel have activity in the second-line treatment of non-small-cell lung cancer (NSCLC), and can be administered as weekly schedules. This phase II randomised study was designed to test the efficacy and toxicity of both taxanes in patients with NSCLC previously treated with platinum-based chemotherapy. PATIENTS AND METHODS: Patients (n = 71) with documented NSCLC were randomised to receive docetaxel (n = 35 patients; 36 mg/m(2)) or paclitaxel (n = 36 patients; 80 mg/m(2)) as a 1 h weekly infusion for 6 weeks followed by a 2-week rest. The cycles were repeated until disease progression or non-acceptable toxicities occurred. RESULTS: Treatment achieved partial response of one versus five patients, median time-to-progression of 74 versus 68 days, and overall survival of 184 versus 105 days, with docetaxel and paclitaxel, respectively. The most common non-haematological toxicities were (docetaxel versus paclitaxel): grade 3/4 pulmonary toxicity in seven versus one patient; grade 2/3 diarrhoea in nine versus five; and grade 3/4 haematological toxicities occurred in two versus four patients. There were no treatment-related deaths. CONCLUSIONS: Docetaxel and paclitaxel administered weekly have discrete efficacy in patients with NSCLC previously treated with platinum-based chemotherapy. The higher non-haematological toxicity of docetaxel, particularly pulmonary toxicity and diarrhoea, is of concern and warrants further investigation.

Cost-minimisation analysis of pegylated liposomal doxorubicin hydrochloride versus topotecan in the treatment of patients with recurrent epithelial ovarian cancer in Spain.

The study consisted of a cost-minimisation analysis since the findings from a multicentre randomised phase III trial showed that pegylated liposomal doxorubicin hydrochloride was at least as efficacious as topotecan. An economic model from the Spanish hospitals perspective was constructed to compare the costs derived from the treatment using both drugs in patients with recurrent epithelial ovarian cancer who failed a first-line platinum-containing regimen. The cost evaluation included direct medical costs: drug, drug administration and costs of managing adverse events. Estimation of resources used in managing adverse events was made retrospectively through an expert panel. Results obtained per patient were: cost of drug and administration, 8647.70 euros for pegylated liposomal doxorubicin hydrochloride and 8519.94 euros for topotecan, while cost of managing adverse events was 967.02 euros in the pegylated liposomal doxorubicin hydrochloride arm and 3304.75 euros for topotecan. The total cost per patient was therefore estimated to be 9614.72 euros for pegylated liposomal doxorubicin hydrochloride and 11 824.69 euros for topotecan, showing that pegylated liposomal doxorubicin hydrochloride produces a cost saving of 2209.97 euros per patient in comparison to topotecan. Sensitivity analyses verified the robustness of the results. These findings suggest that pegylated liposomal doxorubicin hydrochloride is an efficient therapy and can be used as a cost-saving option for treatment of patients with recurrent epithelial ovarian cancer who have failed a first-line platinum-containing regimen.

Estudio fase II de doxorubicina liposomal pegilada (Caelyx®) en carcinoma de ovario avanzado: análisis de eficacia y toxicidad / Phase II study of pegylated liposomal doxorubicin (Caelix®) in advanced ovarian cancer: analysis of efficacy and toxocity

La doxorubicina liposomal pegilada (Caelyx®) es una nueva formulación con un perfil diferente de toxicidad y actividad demostrada en cáncer de ovario avanzado. Nuestro grupo diseñó un estudio fase II de la administración de Caelyx® en pacientes con carcinoma de ovario avanzado recidivadas a platino/paclitaxel. Se administró Caelyx® 50 mg/m2 IV (1 hs.) en ciclos repetidos cada 4 semanas. Fueron incluidas 53 pacientes con adecuada función hematológica, renal y hepática. La mediana de edad fue 60 años (rango 40-78 años), Karnosfky 100 por ciento= 15, 90 por ciento= 29, 80 por ciento= 9 y 76 por ciento de las pacientes habían recibido 2 o más líneas de quimioterapia previa. La mediana de ciclos administradas fue 5 (rango: 1-17) con una intensidad del 87 por ciento de la dosis teórica. En un total de 223 ciclos administrados fueron necesarios 8 por ciento de reducciones y 16 por ciento de retrasos de tratamiento. La principal toxicidad fue no hematológica con eritrodisestesia palmo-plantar grado 1-2: 23 por ciento y grado 3-4: 6 por ciento; mucositis grado 3-4: 3 por ciento y 2 episodios de reacción de hipersensibilidad a la infusión. La toxicidad hematológica fue moderada con neutropenia grado 3-4 en 18 ciclos (8 por ciento) y 3 episodios de neutropenia febril (2 con sepsis a Gram -). La tasa de respuesta global fue 23,5 por ciento con 2 RC y 9 RP. Después de una mediana de seguimiento de 15 meses, la mediana de intervalo libre de progresión y de supervivencia global fueron 5,8 meses (95 por ciento CI: 4,5-7,3) y 14,7 meses (95 por ciento CI: 11,2-18,3), respectivamente. Estos resultados confirman la actividad de Caelyx® en cancer de ovario altamente pretratado y progresadas a la combinación platino-paclitaxel, con una buena tolerancia y excelente manejo terapéutico. (AU)

Combination chemotherapy with cisplatin and 5-fluorouracil 5-day infusion in the therapy of advanced gastric cancer: a phase II trial.

Fifty-six patients with measurable or evaluable advanced gastric cancer were treated with cisplatin, 100 mg/m2 in continuous infusion of 24 hours, and 5-fluorouracil, 1000 mg/m2/day (by continuous 5-day infusion) every 4 weeks. Three patients were found ineligible for the study. A response rate of 41% (22/53) was obtained (95% confidence interval: 28%-54%), with a median duration of remission of 10.2 months and an overall median survival time of 10.6 months. Leukopenia and thrombocytopenia were mild. Nausea and vomiting were common, and 23.5% of the patients had grade 3 stomatitis. Peripheral neuropathy and renal insufficiency increased with the number of cycles, representing the cumulative dose-limiting toxicity. This study indicates that the combination of cisplatin plus 5-fluorouracil is synergistic or at least has additive antitumor activity. We think that this association of 2 drugs should be considered for further phase III clinical trials.