Translating the ABC-02 trial into daily practice: outcome of palliative treatment in patients with unresectable biliary tract cancer treated with gemcitabine and cisplatin.

BACKGROUND: Biliary tract cancer (BTC) is an uncommon cancer with an unfavorable prognosis. Since 2010, the standard of care for patients with unresectable BTC is palliative treatment with gemcitabine plus cisplatin, based on the landmark phase III ABC-02 trial. This current study aims to evaluate the efficacy and safety of gemcitabine and cisplatin in patients with unresectable cholangiocarcinoma and gallbladder cancer in daily practice that meet the criteria for the ABC-02 trial in comparison to patients who did not. METHODS: Patients diagnosed with unresectable BTC between 2010 and 2015 with an indication for gemcitabine and cisplatin were included. We divided these patients into three groups: (I) patients who received chemotherapy and met the criteria of the ABC-02 trial, (II) patients who received chemotherapy and did not meet these criteria and (III) patients who had an indication for chemotherapy, but received best supportive care without chemotherapy. Primary outcome was overall survival (OS) and secondary outcome was progression-free survival (PFS). RESULTS: We collected data of 208 patients, of which 138 (66.3%) patients received first line chemotherapy with gemcitabine and cisplatin. Median OS of 69 patients in group I, 63 patients in group II and 65 patients in group III was 9.6 months (95%CI = 6.7-12.5), 9.5 months (95%CI = 7.7-11.3) and 7.6 months (95%CI = 5.0-10.2), respectively. Median PFS was 6.0 months (95%CI = 4.4-7.6) in group I and 5.1 months (95%CI = 3.7-6.5) in group II. Toxicity and number of dose reductions (p = .974) were comparable between the two chemotherapy groups. CONCLUSION: First-line gemcitabine and cisplatin is an effective and safe treatment for patients with unresectable BTC who do not meet the eligibility criteria for the ABC-02 trial. Median OS, PFS and treatment side effects were comparable between the patients who received chemotherapy (group I vs. group II).

Randomized phase III trial of S-1 versus capecitabine in the first-line treatment of metastatic colorectal cancer: SALTO study by the Dutch Colorectal Cancer Group.

BACKGROUND: Hand-foot syndrome (HFS) is a common side-effect of capecitabine. S-1 is an oral fluoropyrimidine with comparable efficacy to capecitabine in gastrointestinal cancers but associated with a lower incidence of HFS in Asian patients. This study compares the incidence of HFS between S-1 and capecitabine as first-line treatment in Western metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: Patients with previously untreated mCRC and planned treatment with fluoropyrimidine monochemotherapy were randomized 1 : 1 to receive either capecitabine (1250 mg/m2 orally for patients <70 years; 1000 mg/m2 for patients ≥70 years, twice daily on days 1-14) or S-1 (30 mg/m2 orally twice daily on days 1-14) in 3-weekly cycles, with bevacizumab optional in both groups. The primary endpoint was the incidence of any grade HFS, as assessed by both physicians and patients (diaries). Secondary endpoints included grade 3 HFS, other toxicities, relative dose intensity, progression-free survival, response rate and overall survival. RESULTS: A total of 161 patients were randomized in 27 centres. The incidence of any grade HFS as assessed by physicians was 73% in the capecitabine group (n = 80) and 45% in the S-1 group (n = 80) [odds ratio (95% confidence interval) 0.31 (0.16-0.60), P = 0.0005]. The incidence of grade 3 HFS was 21% and 4% (P = 0.003), respectively. Patient-assessed any grade HFS was 84% and 58%, respectively (P = 0.004). Grade 3 anorexia was more common in the S-1 group (3% versus 13%, P = 0.03). Median relative dose intensity was 88% in the capecitabine group and 95% in the S-1 group (P = 0.026). There were no statistically significant differences in median progression-free survival, response rate and overall survival rates. CONCLUSION: Treatment with S-1 in Western mCRC patients is associated with a significantly lower incidence of HFS compared with capecitabine, with comparable efficacy. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT01918852.

Effect of a prediction tool and communication skills training on communication of treatment outcomes: a multicenter stepped wedge clinical trial (the SOURCE trial).

Background: For cancer patients to effectively engage in decision making, they require comprehensive and understandable information regarding treatment options and their associated outcomes. We developed an online prediction tool and supporting communication skills training to assist healthcare providers (HCPs) in this complex task. This study aims to assess the impact of this combined intervention (prediction tool and training) on the communication practices of HCPs when discussing treatment options. Methods: We conducted a multicenter intervention trial using a pragmatic stepped wedge design (NCT04232735). Standardized Patient Assessments (simulated consultations) using cases of esophageal and gastric cancer patients, were performed before and after the combined intervention (March 2020 to July 2022). Audio recordings were analyzed using an observational coding scale, rating all utterances of treatment outcome information on the primary outcome-precision of provided outcome information-and on secondary outcomes-such as: personalization, tailoring and use of visualizations. Pre vs. post measurements were compared in order to assess the effect of the intervention. Findings: 31 HCPs of 11 different centers in the Netherlands participated. The tool and training significantly affected the precision of the overall communicated treatment outcome information (p = 0.001, median difference 6.93, IQR (-0.32 to 12.44)). In the curative setting, survival information was significantly more precise after the intervention (p = 0.029). In the palliative setting, information about side effects was more precise (p < 0.001). Interpretation: A prediction tool and communication skills training for HCPs improves the precision of treatment information on outcomes in simulated consultations. The next step is to examine the effect of such interventions on communication in clinical practice and on patient-reported outcomes. Funding: Financial support for this study was provided entirely by a grant from the Dutch Cancer Society (UVA 2014-7000).

A comparison of amodiaquine and sulfadoxine-pyrimethamine as first-line treatment of falciparum malaria in Kenya.

A randomized 14-day study in vivo compared the response of Plasmodium falciparum malaria to amodiaquine (35 mg/kg) and sulfadoxine-pyrimethamine (sulfadoxine, 25 mg/kg) in symptomatic outpatients at 2 sites in northern and western Kenya during 1993. Of the 239 patients recruited, 181 (76%) completed the study [84 (46%) on amodiaquine and 97 (54%) on sulfadoxine-pyrimethamine]. There were no significant differences in the parasitological, clinical or haematological responses between the 2 drug groups in both areas, with 18.5% resistance to amodiaquine versus 9.5% for sulfadoxine-pyrimethamine in the north and 35.1% against amodiaquine versus 34.5% for sulfadoxine-pyrimethamine in the west. In both sites defervescence was significantly more rapid with amodiaquine (P < 0.05) and true clinical failure (symptomatic illness with recurrent parasitaemia) was unusual (9%). As high-level resistance to chloroquine is widespread, both drugs are valuable alternatives. However, the significantly higher levels of resistance in the west may be a sign of the increased drug pressure in this holoendemic area and send an important warning concerning resistance to sulfadoxine-pyrimethamine.

[Meperidine (pethidine) outdated as analgesic in acute pancreatitis]. / Pethidine achterhaald als pijnstiller bij acute pancreatitis.

The most important symptom in acute pancreatitis is pain. This pain often is so severe that treatment is started with opioid analgesics. In daily practice meperidine is often the analgesic of first choice because it is supposed to cause less spasm of the M. sphincter ampullae hepatopancreaticae (sphincter of Oddi). Drawbacks of the use of meperidine compared with other opiods are myoclonias, tremors and convulsions due to accumulation of the metabolite norpethidine, and hypotension, tachycardia and erythema due to release of more histamine from mast cells. From literature study it appeared that all opioids have a spasmogenic effect on the sphincter of Oddi, that there are no good arguments to assume that this effect is less when meperidine is used, and that there is no good evidence that this spasmogenic effect of opioid analgesics influences the course of acute pancreatitis in an unfavourable way. Since the profile of effects and side effects of meperidine is unfavourable, we prefer the use of opioids with a larger therapeutic width.