Please read this abstract from a clinical trial:  Randomised phase-II trial of CAPIRI (capecitabine, irinotecan) plus bevacizumab vs FOLFIRI (folinic acid, 5-fluorouracil, irinotecan) plus bevacizumab as first-line treatment of patients with unresectable/metastatic colorectal cancer (mCRC) Background: To compare the efficacy and safety of CAPIRI+bevacizumab (Bev) in comparison with FOLFIRI+Bev as first-line treatment for patients with metastatic colorectal cancer (mCRC). Methods: Patients were randomised to receive either FOLFIRI plus Bev 5 mg/kg every 2 weeks (Arm-A) or CAPIRI plus Bev 7.5 mg/kg every 3 weeks (Arm-B). Results: Three hundred thirty-three patients (Arm-A=167; Arm-B=166) were enrolled into the study. No difference was observed in median progression-free survival (PFS) (10.0 and 8.9 months; P=0.64), overall survival (25.7 and 27.5 months; P=0.55) or response rates (45.5 and 39.8.7%; P=0.32) for FOLFIRI-Bev and CAPIRI-Bev, respectively. Patients treated with CAPIRI-Bev presented significantly higher incidence of diarrhoea (P=0.005), febrile neutropenia (P=0.003) and hand-foot skin reactions (P=0.02) compared with patients treated with FOLFIRI-Bev. Treatment delays (P=0.05), dose reduction (P

PBL Assessment Please review the following case notes and protocol prior answering the questions below:   Oncology PBL Case 4.pdf you can open this file in another window (right click the link – open in new tab) Case 4 protocol Capecitabine and Oxaliplatin 21 day cycle CAPOX Colorectal Cancer.pdf you can open this file in another window (right click the link – open in new tab)   Reference sources:   Capecitabine SPC: https://www.medicines.org.uk/emc/product/14591/smpc#gref Oxaliplatin SPC: https://www.medicines.org.uk/emc/product/3024/smpc#gref Dose banding capecitabine: https://www.england.nhs.uk/wp-content/uploads/2018/05/national-tables-capecitabine-v1.pdf Dose banding oxalitplatin: https://www.england.nhs.uk/wp-content/uploads/2018/04/national-tables-5-mgml-v3.pdf Formulae:    Body surface area:  Creatinine clearance (Cockcroft Gault):  Constant: 1.04 (women); 1.23 (men) 

Following Cycle 3, the patient develops Grade 3 diarrhoea. What action should be taken? (3 marks) The common toxicities criteria are outlined below: Grade 1: Mild toxicity – often asymptomatic or mild symptoms, no intervention needed, treatment can usually continue. Grade 2: Moderate toxicity – symptoms more pronounced, may need intervention (e.g., medication) Grade 3: Severe toxicity – significant symptoms, may require hospitalisation or intensive intervention; likely to lead to treatment delay, dose reduction or even temporary cessation. Grade 4: Life-threatening toxicity – urgent medical intervention required, serious risk to life, definite treatment interruption/adjustment. Grade 5: Death related to the adverse event/toxicity.

Calculate the appropriate initial dose of Carboplatin and Paclitaxel for the patient. (8 marks) 

Prior to the 2nd cycle the patient’s blood results are as below:   How would these results affect the patient’s next cycle of systemic anti-cancer treatment? (4 marks) 

Please read this abstract from a clinical trial:  Preoperative Chemoradiotherapy for Oesophageal or Junctional Cancer Background The role of neoadjuvant chemoradiotherapy in the treatment of patients with oesophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population. Methods We randomly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. Results From March 2004 through December 2008, we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%) had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large-cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most common major hematologic toxic effects in the chemoradiotherapy–surgery group were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the chemoradiotherapy–surgery group versus 69% in the surgery group (P

Prior to the 3rd week of treatment the patient’s blood results are as below:    How would these results affect the patient’s next cycle of systemic anti-cancer treatment? (6 marks) 

Please read this abstract from a clinical trial:  Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial Background Patients with advanced non-squamous non-small-cell lung cancer (NSCLC) benefit from pemetrexed maintenance therapy after induction therapy with a platinum-containing, non-pemetrexed doublet. The PARAMOUNT trial investigated whether continuation maintenance with pemetrexed improved progression-free survival after induction therapy with pemetrexed plus cisplatin. Methods In this double-blind, multicentre, phase 3, randomised placebo-controlled trial, patients with advanced non-squamous NSCLC aged 18 years or older, with no previous systemic chemotherapy for lung cancer, with at least one measurable lesion, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 participated. Before randomisation, patients entered an induction phase which consisted of four cycles of induction pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) on day 1 of a 21-day cycle. Patients who did not progress after completion of four cycles of induction and who had an ECOG performance status of 0 or 1 were stratified according to disease stage (IIIB or IV), ECOG performance status (0 or 1), and induction response (complete or partial response, or stable disease), and randomly assigned (2:1 ratio) to receive maintenance therapy with either pemetrexed (500 mg/m2 every 21 days) plus best supportive care or placebo plus best supportive care until disease progression. Randomisation was done with the Pocock and Simon minimisation method. Patients and investigators were masked to treatment assignment. The primary endpoint was progression-free survival in the intention-to-treat population. Findings Of the 1022 patients enrolled, 939 participated in the induction phase. Of these, 539 patients were randomly assigned to receive continuation maintenance with pemetrexed plus best supportive care (n=359) or with placebo plus best supportive care (n=180). Among the 359 patients randomised to continuation maintenance with pemetrexed, there was a significant reduction in the risk of disease progression over the placebo group (HR 0·62, 95% CI 0·49–0·79; p

Prior to the 4th cycle the patient’s blood results are as below:   How would these results affect the patient’s next cycle of systemic anti-cancer treatment? (4 marks) 

The infant brain (let’s say 6 months) is incapable of forming memories of any type.