Anthracycline-based triplets do not improve the efficacy of platinum-fluoropyrimidine doublets in first-line treatment of advanced gastric cancer: real-world data from the AGAMEMON National Cancer Registry.

BACKGROUND: Although anthracycline-based triplets are one of the most widely used schedules to treat advanced gastric cancer (AGC), the benefit of including epirubicin in these therapeutic combinations remains unknown. This study aims to evaluate both the efficacy and tolerance of triplets with epirubicin vs. doublets with platinum-fluoropyrimidine in a national AGC registry. METHODS: Patients with AGC treated with polychemotherapy without trastuzumab at 28 hospitals in Spain between 2008 and 2016 were included. The effect of anthracycline-based triplets against doublets was evaluated by propensity score matching (PSM) and Cox proportional hazards (PH) regression. RESULT: A total of 1002 patients were included (doublets, n = 653; anthracycline-based triplets, n = 349). The multivariable Cox PH regression failed to detect significantly increased OS in favor of triplets with anthracyclines: HR 0.90 (95% CI, 0.78-1.05), p = 0.20035. After PSM, the sample contained 325 pairs with similar baseline characteristics. This method was also unable to reveal an increase in OS: 10.5 (95% CI, 9.7-12.3) vs. 9.9 (95% CI, 9.2-11.4) months, HR 0.91 (CI 95%, 0.76-1.083), and (log-rank test, p = 0.226). Response rates (42.1 vs. 33.1%, p = 0.12) and PFS (HR 0.95, CI 95%, 0.80-1.13, log-rank test, p = 0.873) were not significantly higher with epirubicin-based regimens. The triplets were associated with greater grade 3-4 hematological toxicity, and increased hospitalization due to toxicity by 68%. The addition of epirubicin is viable, but 23.7% discontinued treatment because of adverse effects or patient decision. CONCLUSION: Anthracyclines added to platinum-fluoropyrimidine doublets did not improve the response rate or survival outcomes in patients with AGC but entailed greater toxicity.

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab.

BACKGROUND: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. METHODS: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. RESULTS: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5-6.6), 9.4 (95% CI, 8.5-10.6), and 14 months (95% CI, 11.8-16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3-8.1), 12.7 (95% CI, 11.3-14.3), and 18.3 months (95% CI, 14.6-24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591-0.631) and 0.673 (95% CI, 0.636-0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). CONCLUSIONS: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design.

Optimal duration of first-line chemotherapy for advanced gastric cancer: data from the AGAMENON registry.

BACKGROUND: The optimal duration of first-line chemotherapy for patients with advanced gastric cancer is unknown. Diverse clinical trials have proposed different strategies including limited treatment, maintenance of some drugs, or treatment until progression. METHOD: The sample comprises patients from the AGAMENON multicenter registry without progression after second evaluation of response. The objective was to explore the optimal duration of first-line chemotherapy. A frailty multi-state model was conducted. RESULTS: 415 patients were divided into three strata: discontinuation of platinum and maintenance with fluoropyrimidine until progression (30%, n = 123), complete treatment withdrawal prior to progression (52%, n = 216), and full treatment until progression (18%, n = 76). The hazard of tumor progression decreased by 19% per month with the full treatment regimen. However, we found no evidence that fluoropyrimidine maintenance (hazard ratio [HR] 1.07, confidence interval [CI] 95%, 0.69-1.65) worsened progression-free survival (PFS) with respect to treatment until progression. Predictive factors for PFS were ECOG performance status, ≥ 3 metastatic sites, prior tumor response, and bone metastases. Toxicity grade 3/4 was more common in those who continued the full treatment until progression vs fluoropyrimidine maintenance (16% vs 6%). CONCLUSION: The longer duration of the full initial regimen exerted a protective effect on the patients of this registry. Platinum discontinuation followed by fluoropyrimidine maintenance yields comparable efficacy to treatment up to PD, with a lower rate of serious adverse events.

[Cross reactivity among proton pump inhibitors: does it exits?]. / 'Existe reactividad cruzada entre inhibidores de la bomba de protones?

BACKGROUND: There has been little research into adverse reactions to proton pump inhibitors (omeprazole and its analogs) of suspected allergic etiology. We found nine studies in the medical literature and only two of these describe cross reactivity between proton pump inhibitors detected by skin prick tests. CASE REPORT: We present a 24-year-old woman who twice developed total body pruritus and urticaria with facial angioedema 1-2 hours after ingesting an omeprazole capsule. In the second episode the patient also reported the sensation of having a lump in her throat. METHODS: Skin prick and intradermal tests were performed with omeprazole, pantoprazole, and lansoprazole, which were positive for the three proton pump inhibitors. For ethical reasons, oral challenge testing was not performed. CONCLUSION: The clinical picture and the positive skin test results suggest an IgE-mediated mechanism. Skin prick tests may be useful for the diagnosis of cases of suspected allergy to omeprazole and its analogs. We found cross reactivity between three proton pump inhibitors detected by skin tests.

¿Existe reactividad cruzada entre inhibidores de la bomba de protones? / Cross reactivity among proton pump inhibitors: does it exits?

Antecedentes: Los casos descritos sobre reacciones adversas a los inhibidores de la bomba de protones (omeprazol y análogos) con sospecha de etiología alérgica son escasos, encontrando un total de nueve trabajos en la literatura médica. Únicamente en dos de ellos se ha descrito la existencia de reactividad cruzada entre varios miembros del grupo mediante pruebas cutáneas. Caso clínico: Se trata de una mujer de 24 años que presentó en dos ocasiones prurito y urticaria generalizados, con angioedema facial en un intervalo de 1-2 horas tras la toma de omeprazol por vía oral; en el segundo episodio refiere además sensación de cuerpo extraño en garganta. Métodos: Se realizan pruebas cutáneas por prick e intradermorreacción con omeprazol, lansoprazol y pantoprazol, con resultado positivo para los tres fármacos. No se realiza provocación oral por razones éticas. Conclusión: El desarrollo del cuadro clínico y la positividad de los tests cutáneos sugieren un mecanismo mediado por Ig E. Destaca la validez de las pruebas cutáneas en el diagnóstico de los casos de sospecha de alergia a omeprazol y análogos. Hemos encontrado la existencia de reactividad cruzada entre los inhibidores de la bomba de protones, mediante la positividad de pruebas cutáneas (AU)

Background: There has been little research into adverse reactions to proton pump inhibitors (omeprazole and its analogs) of suspected allergic etiology. We found nine studies in the medical literature and only two of these describe cross reactivity between proton pump inhibitors detected by skin prick tests. Case report: We present a 24-year-old woman who twice developed total body pruritus and urticaria with facial angioedema 1-2 hours after ingesting an omeprazole capsule. In the second episode the patient also reported the sensation of having a lump in her throat. Methods: Skin prick and intradermal tests were performed with omeprazole, pantoprazole, and lansoprazole, which were positive for the three proton pump inhibitors. For ethical reasons, oral challenge testing was not performed. Conclusion: The clinical picture and the positive skin test results suggest an IgE-mediated mechanism. Skin prick tests may be useful for the diagnosis of cases of suspected allergy to omeprazole and its analogs. We found cross reactivity between three proton pump inhibitors detected by skin tests (AU)