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Peptide receptor radionuclide therapy (PRRT) is an increasingly used treatment for unresectable neuroendocrine tumours (NETs) that express somatostatin receptors. Normal pituitary tissue expresses somatostatin receptors so patients receiving PRRT may be at risk of developing hypopituitarism. The aim was to assess the prevalence of clinically significant hypopituitarism a minimum of 2 years following radioisotope therapy for metastatic NET. This was a multicentre study (Australia and New Zealand). Sixty-six patients with unresectable NETs were included-34 had received PRRT and 32 comparison patients. Median follow-up after PRRT was 68 months. Male hypogonadism was the most common hormonal abnormality (16 of 38 men [42%]) from the total cohort. Of these, seven men had primary hypogonadism (five from PRRT group) and nine had secondary hypogonadism (six in PRRT group). There was no difference in either male hypogonadism or other hormonal dysfunction between patients who had received PRRT and those that had not. Patients who have received PRRT out to 68 months following treatment do not show concerning hypopituitarism although there may be the suggestion of growth hormone deficiency developing. However, hypogonadism is common in men with NETs so the gonadal axis should be assessed in men with suggestive symptoms as the treatment of testosterone deficiency may improve the quality of life.Copyright © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Purpose: SIRFLOX was a randomized, multicenter trial designed to assess the efficacy and safety of adding selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy in patients with previously untreated metastatic colorectal cancer. Patients and Methods: Chemotherapy-naive patients with liver metastases plus or minus limited extrahepatic metastases were randomly assigned to receive either modified FOLFOX (mFOLFOX6; control) or mFOLFOX6 plus SIRT (SIRT) plus or minus bevacizumab. The primary end point was progression-free survival (PFS) at any site as assessed by independent centralized radiology review blinded to study arm. Result(s): Between October 2006 and April 2013, 530 patients were randomly assigned to treatment (control, 263; SIRT, 267).Median PFS at any site was 10.2 v 10.7months in control versus SIRT (hazard ratio, 0.93; 95% CI, 0.77 to 1.12; P = .43). Median PFS in the liver by competing risk analysis was 12.6 v 20.5 months in control versus SIRT (hazard ratio, 0.69; 95%CI, 0.55 to 0.90; P = .002). Objective response rates (ORRs) at any site were similar (68.1% v 76.4%in control v SIRT; P = .113). ORR in the liver was improved with the addition of SIRT (68.8%v 78.7% in control v SIRT; P = .042). Grade >= 3 adverse events, including recognized SIRT-related effects, were reported in 73.4% and 85.4% of patients in control versus SIRT. Conclusion(s): The addition of SIRT to FOLFOX-based first-line chemotherapy in patients with liver-dominant or liveronly metastatic colorectal cancer did not improve PFS at any site but significantly delayed disease progression in the liver. The safety profile was as expected and was consistent with previous studies.Copyright © 2016 by American Society of Clinical Oncology.

Background: AMG 386, an investigational peptide-Fc fusion protein, inhibits angiogenesis by preventing the interaction of angiopoietin-1 and -2 with their receptor, Tie2. This study estimated the efficacy and assessed the safety of AMG 386 plus FOLFIRI in patients with mCRC. Method(s): Eligible patients (>=18 years) had adenocarcinoma of the colon or rectum with progression within 6 months of having received 1 prior 5-FU- and oxaliplatin-based chemotherapy regimen for metastatic disease, ECOG status 0-1, and >=1 measurable lesion per RECIST. Patients were randomized 2:1 to receive FOLFIRI IV Q2W plus either (Arm A) AMG 386 10 mg/kg IV QW or (Arm B) placebo IV QW. Randomization was stratified by ECOG performance status (0 vs 1). The study was designed to estimate the treatment effect as measured by investigator-assessed progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) per RECIST, adverse events (AEs), and pharmacokinetics (PK). Result(s): 144 patients were randomized (Arms A/B, N=95/49). The median PFS (80% CI) in Arms A and B was 3.5 (2.9-4.2) and 5.2 (3.8-5.5) months, respectively. Based on a Cox regression model stratified by ECOG status, the hazard ratio (HR) (80% CI) for Arm A vs B was 1.23 (0.94-1.61; P=0.33). In Arms A/B (n=84/45; 16 patients were too early to evaluate for response), the ORR (80% CI) was 14% (10-20) in Arm A and 0% (0-5) in Arm B. Median Cmax and Cmin values of AMG 386 at steady state following coadministration with FOLFIRI were generally similar to those reported for AMG 386 monotherapy. Coadministration of FOLFIRI with AMG 386 did not affect the PK of AMG 386. Based on sparse PK sampling the SN-38 and 5-FU exposures were approximately 50% lower with AMG 386 coadministration. The incidence of AEs was similar between treatment arms. Most frequent AEs included diarrhea (Arm A/B, 47/ 41%; grade >=3, 4/0%), nausea (44/37%; grade >=3, 0/2%), neutropenia (41/57%; grade >=3, 31/41%), asthenia (31/33%; grade

Background: This phase 2 study evaluated trebananib (AMG 386), an investigational peptide-Fc fusion protein that neutralises the interaction between angiopoietins-1/2 and the Tie2 receptor, plus FOLFIRI as second-line treatment for patients with metastatic colorectal cancer. Method(s): Patients had adenocarcinoma of the colon or rectum with progression within 6 months of receiving only one prior fluoropyrimidine/oxaliplatin-based chemotherapy regimen for metastatic disease. All patients received FOLFIRI and were randomised 2: 1 to also receive intravenous trebananib 10 mg kg-1 once weekly (QW) (Arm A) or placebo QW (Arm B). The primary end point was investigator-assessed progression-free survival (PFS). Result(s): One hundred and forty-four patients were randomised (Arms A/B, n=95/49). Median PFS in Arms A and B was 3.5 and 5.2 months (hazard ratio (HR) 1.23; 95% CI, 0.81-1.86; P=0.33) and median overall survival (OS) was 11.9 and 8.8 months, respectively (HR 0.90; 95% CI; 0.53-1.54; P=0.70). Objective response rate (ORR) was 14% and 0% in Arms A and B, respectively. Incidence of grade >=3 adverse events was similar between treatment arms (Arm A, 61%; Arm B, 65%) and included pulmonary embolism (1%/4%), deep vein thrombosis (5%/2%), and hypertension (1%/0%). Conclusion(s): Administration of trebananib plus FOLFIRI did not prolong PFS compared with placebo plus FOLFIRI. Toxicities were manageable and consistent with those known for FOLFIRI and trebananib. © 2013 Cancer Research UK. All rights reserved.

Background:Cetuximab can reverse chemotherapy resistance in colorectal cancer. This study evaluated the efficacy and safety of the combination of docetaxel and cetuximab as a second-line treatment in docetaxel-refractory oesophagogastric cancer. Method(s):Patients received docetaxel 30 mg m-2 on days 1 and 8, every 3 weeks and cetuximab 400 mg m-2 on day 1, then 250 mg m-2 weekly. Biomarker mutation analysis was performed. Result(s):A total of 38 patients were enrolled. Response rates were PR 6% (95% CI 2-19%), s.d. 43% (95% CI 28-59%). Main grade 3/4 toxicities were febrile neutropenia, anorexia, nausea, diarrhoea, stomatitis, and acneiform rash. Median progression-free and overall survival were 2.1 and 5.4 months, respectively. A landmark analysis showed a trend to improved survival times with increased grade of acneiform rash. No KRAS, BRAF or PIK3CA mutations were observed. Conclusion(s):Cetuximab and docetaxel achieve modest responses rates, but maintain comparable survival times to other salvage regimens with low rates of toxicity. © 2013 Cancer Research UK.

Background: The CO.20 trial randomized pts with K-RAS WT chemotherapy refractory mCRC to receive CET + BRIV (Arm A) or CET + placebo (Arm B). Although overall survival (primary endpoint) was not significantly improved (HR=0.88, p=0.12) in this heavily pre-treated population, progression free survival (PFS) favoured Arm A (HR=0.72 p<0.0001). Method(s): Patients with K-RAS WT mCRC previously treated with or with contraindications to a fluoropyrimidine, irinotecan, and oxaliplatin were randomized to a loading dose of IV CET followed by weekly IV CET + BRIV 800 mg PO daily or CET + placebo daily. QoL, a secondary endpoint, was assessed using the EORTC QLQ-C30 at baseline and at 2, 4, 6, 8, 12, 16 and 24 weeks until progression or clinical deterioration. Co-primary QoL endpoints were defined a priori as definitive deterioration (first worsening from baseline of >=10 points) on the physical function (PF) and Global scales. Time to QoL deterioration (DET) was measured from randomization using the Hochberg procedure to adjust for multiple testing. Result(s): 721 (358 Arm A) of 750 randomized pts were assessable for QoL. QoL compliance did not differ by arm and declined in follow-up from 87% to 47% over time. Baseline Global and PF scores did not differ by arm. Median time to QoL DET was 1.6 vs 1.1 mo for Global (p=0.02) and 5.6 vs 1.7 mo. for PF (p<0.0001) in Arm B vs A, respectively. Secondary QoL response evaluation showed a greater proportion of patients on Arm A to have worsening on the PF (31 vs 17% at 6 wks) and cognitive functioning scales, and on the fatigue, nausea, appetite and diarrhea symptom scales. Clinical adverse events >= Grade 3 were more common on Arm A than B including fatigue (25 vs 10%), hypertension, rash, diarrhea, abdominal pain, dehydration and anorexia. Conclusion(s): Despite a PFS benefit, the combination of CET + BRIV worsened time to QoL DET on the PF and Global scales of EORTC QLQ-C30 in pts with chemotherapy refractory K-RAS WT mCRC. This res

Prostate cancer is a leading cause of cancer death, frequently associated with widespread bone metastases. We report two cases of hypocalcemia following the first dose of denosumab in metastatic hormone refractory prostate cancer, the first case requiring 26. days of intravenous calcium therapy. This is the first report of prolonged hypocalcemia following denosumab in a patient with normal renal function. © 2013 .

Standard chemoradiotherapy with infusional 5FU for locally advanced pancreatic cancer (LAPC) has limited efficacy in this disease. The combination of Capecitabine (Cap) and Gemcitabine (Gem) are synergistic and are potent radiosensitisers. The aim of this phase I trial was thus to determine the highest administered dose of the Cap plus Gem combination with radical radiotherapy (RT) for LAPC. Patients had LAPC, adequate organ function, ECOG PS 0-1. During RT, Gem was escalated from 20-50 mg m-2 day-1 (twice per week), and Cap 800-2000 mg m-2 day-1 (b.i.d, days 1-5 of each week). Radiotherapy 50.4 Gy/28 fractions/5.5 weeks, using 3D-conformal techniques. Three patients were entered to each dose level (DL). Dose-limiting toxicity(s) (DLTs) were based on treatment-related toxicities. Twenty patients were accrued. Dose level (DL) 1: Cap/Gem; 800/20 mg m -2 day-1 (3 patients), DL2: 1000/20 (12 patients), DL3: 1300/30 (5 patients). Dose-limiting toxicities were observed in DL3; grade 3 dehydration (1 patient) and grade 3 diarrhoea and dehydration (1 patient). Dose level 2 was the recommend phase 2 dose. Disease control rate was 75%: PR=15%, SD=60%. Median overall survival was 11.2 months. The addition of Cap and Gem to radical RT was feasible and active and achieved at relatively low doses. © 2009 Cancer Research UK.

Background: Bevacizumab is an antiangiogenic mAb with efficacy against several cancers, but it is associated with risk of arterial thromboembolism (ATE). Further data are needed to determine the safety of bevacizumab. Patients and Methods: We recorded grade 3, 4, or 5 ATE events and other data (including age, baseline cardiovascular risk factors, history of ATE, and aspirin use) from 471 patients with metastatic colorectal cancer in the MAX (Mitomycin, Avastin, Xeloda) trial of capecitabine monotherapy versus capecitabine with bevacizumab with or without mitomycin C. Result(s): Bevacizumab-treated patients had 12 grade 3, 4, or 5 ATEs (3.8% incidence). ATEs occurred in 2.1% of patients >65 years, 5% of those with a history of ATE, and 5% of those with cardiac risk factors. Age, history of ATE, or vascular risk factors did not increase risk. Aspirin users had a higher incidence than nonusers (8.9% versus 2.7%) but had higher rates of vascular risk factors. Conclusion(s): Bevacizumab was associated with a modestly higher risk of ATE, but safety was not significantly worse in older patients or patients with a history of ATE or vascular risk factors. The effect of aspirin in preventing ATE in patients receiving bevacizumab could not be determined from this study. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Purpose: The objective of this study was to conduct a randomised phase II study in second-line metastatic colorectal cancer with the purpose of confirming preliminary clinical data indicating that the formulation of irinotecan with the drug carrier, hyaluronan (HA) reduced toxicity of the drug. Method(s): Irinotecan-naive patients were randomized to receive either irinotecan (350 mg/m2) or HA-Irinotecan (HA 1,000 mg/m2 and irinotecan at 350 mg/m2) every 3 weeks for a maximum of eight cycles. Result(s): Seventy-six patients (41 HA-Irinotecan and 35 irinotecan-alone) were enrolled. There was no significant difference in any individual, or overall, grade 3 or 4 toxicity. There was a trend for increased diarrhea in the HA-Irinotecan-treated patients (20 versus 9%; P = 21), potentially explained by a disproportionate number of baseline toxicity-associated risk factors in this treatment group. The median number of cycles completed was six for HA-Irinotecan patients and two for irinotecan-alone patients (P = 0.005). When compared to the control arm, HA-Irinotecan patients had a significantly longer median progression-free survival of 5.2 versus 2.4 months (P = 0.017) and time to treatment failure (4 vs. 1.8 months; P = 0.007). Median overall survival was 10.1 months for HA-Irinotecan compared to 8.0 months for irinotecan patients (P = 0.196). Conclusion(s): Further studies are required to define the safety of the formulation of irinotecan with HA. While this study was not adequately powered to demonstrate survival differences, these phase II data indicated HA-Irinotecan to be a promising therapy demonstrating improved efficacy compared to irinotecan-alone. © 2010 Springer-Verlag.

Background: Pmab, a fully human monoclonal antibody targeting EGFR, has demonstrated activity in combination with FOLFIRI for second-line treatment of mCRC (study 181). Here, we describe the results of a prespecified subgroup analysis of study 181 to evaluate the efficacy of pmab plus FOLFIRI vs FOLFIRI alone in pts who received prior bev. Method(s): Prior bev use for mCRC (yes vs no) was a predefined baseline covariate and stratification factor in study 181. A subgroup analysis was conducted to evaluate the treatment effect of pmab plus chemotherapy on progression-free survival (PFS), overall survival (OS), and tumor response rate in pts with wild-type (WT) KRAS tumors who received prior bev for mCRC. Result(s): 115 pts (from 20 countries) with WT KRAS tumors who had received prior bev were identified. Worst grade of 3 or 4 adverse events (AE) occurred in 73% of pts in the pmab+FOLFIRI arm vs 57% in FOLFIRI arm. Worst grade 3-4 AEs of interest included: skin toxicity (tox [35 vs 5%]); eye tox (7 vs 0%); nail tox (5 vs 0%); diarrhea (9 vs 8%); stomatitis/oral mucositis (7 vs 2%); pulmonary tox (0 vs 3% [and one grade 5 in the FOLFIRI arm]); vascular tox (2 vs 15%); hypomagnesemia (4 vs 0%); cardiac tox (0 vs 3%); and hypocalcemia (2 vs 0%). Grade 5 AEs occurred in 2% and 3% of pts, respectively. Median PFS and OS were numerically longer, and there was a significantly higher overall response rate (ORR) in the pmab+FOLFIRI arm vs FOLFIRI (Table). Conclusion(s): Pts with mCRC and WT KRAS tumors who progress after therapy with bev may benefit from second-line therapy with pmab+FOLFIRI. (Table presented).

Background: The CO.17 trial demonstrated that the addition of cetuximab monotherapy (C) to best supportive care (BSC) improves OS and progression-free survival (PFS) in patients (pts) with ACRC. We compared tumour measurement as a continuous variable and visualized by waterfall plot vs. categorized as response based on RECIST as potential early predictors of OS benefit. Method(s): Of the 572 randomized, 216 pts on C and 142 on BSC had tumor assessment at baseline and 8 weeks and are included in this analysis. Response at 8 weeks was assessed using standard RECIST criteria and categorised as partial response, stable disease or progressive disease. Continuous tumour size measurement was also assessed using waterfall plot, The absolute difference in logarithm transformed sum of the longest tumor diameters (LSLD) between 8 weeks and baseline were calculated for the entire group and the KRAS wild-type (WT) and mutant (MUT) subgroups and correlated with OS in a multivariate analysis including difference in LSLD, RECIST response and other prognostic factors as covariates. Result(s): The increase of tumor size (cm) from baseline of pts treated by C was significantly smaller than those that received BSC (mean difference in LSLD 0.02 vs. 0.23; p < 0.0001), and this remained significant after adjusting for baseline prognostic factors (p<0.0001). In a multivariate analysis of pts treated by C, difference in LSLD was significantly associated with OS (HR 14.84, per ln(cm) of increase, 95% CI 4.31 to 51.08; p<0.0001), whilst RECIST defined response was not. Results were similar for WT pts: HR 14.30 per ln(cm) of increase in LSLD, 95% CI 1.32 to 96.5; p=0.03. For MUT pts, neither change in LSLD nor RECIST response was associated with OS. Conclusion(s): Change of tumor size at 8 weeks following commencement of C using a waterfall plot analysis was a better predictor of OS than standard RECIST categories. This may be a better early signal of treatment efficacy for molecular targeted

Background: AMG 386, a first-in-class investigational peptide-Fc fusion protein (peptibody), blocks angiogenesis via inhibiting the interaction between angiopoietins-1 and -2 and the Tie2 receptor. We evaluated the efficacy and tolerability of AMG 386 or placebo plus CX in the first-line treatment of metastatic gastroesophageal adenocarcinoma. Method(s): Pts with confirmed metastatic adenocarcinoma of the stomach, gastroesophageal junction or distal esophagus were randomized 1:1:1 to receive CX (cisplatin, 80 mg/m2 IV Q3W; capecitabine, 1,000 mg/m2 orally BID for 14 days Q3W) plus AMG 386 10 mg/kg (Arm A), 3 mg/kg (Arm B), or placebo (Arm C) IV QW. The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR; in pts with measurable disease), adverse events (AEs), and pharmacokinetics (PK). Result(s): 171 pts were randomized (Arm A/B/C, n = 56/59/56). Efficacy results are summarized in the table. The incidence of grade >= 3 AEs in Arms A/B/C was 80/84/75%. Serious AEs occurred in 73/60/47% and serious AEs grade >= 3 in 66/60/43% of pts. AEs in Arms A/B/C included abdominal pain (30/40/17%; grade >= 3, 18/3/4%), peripheral edema (13/29/6%; grade >= 3, 0/2/0%), venous thromboembolic events (20/22/19%; grade >= 3, 20/19/17%), and pulmonary embolism (9/3/15%; grade >= 3, 9/2/13%). Median AMG 386 Cmax andCmin values at steady state after CX coadministration were dose-proportional. Coadministration with CX did not markedly affect AMG 386 exposure. Conclusion(s): In this study, AMG 386 plus CX did not significantly improve PFS or ORR over placebo plus CX in this patient population. The toxicity of the combination of AMG 386 plus CX, compared with placebo, was greater but manageable. No unexpected AEs occurred.

Aim: CVCs are often used to deliver chemotherapy to patients with cancer. The aim of our study was to compare safety of the CVCs (PICC and PORT) in patients with non-hematological malignancies. Method(s): Eligible patients from three Australian hospitals were prospectively randomised (1:1) and allocated to either a Groshong PICC or a single chamber PORT device. Data was collected every 3 wks from CVC insertion up to treatment completion, removal of device or disease progression, whichever occurred earlier. Result(s): 70 patients (36 males and 34 females) were randomised at 3 centres between Dec 2004- Dec 2009 to PICC (36/70) or PORT (34/70). One patient from each arm withdrew consent prior to CVC insertion. Mean age was comparable in both arms (62 yrs in PICC v 61 yrs in PORT). Prolonged chemotherapy infusion was the commonest indication for CVC insertion (70% in PICC and 74% in PORT). 60% of patients had metastatic disease and colorectal cancer was the leading diagnosis overall (46 out of 70 patients). There were no procedure related complications. Median time to insertion (time from randomisation to CVC insertion) was 7 and 12 days for PICC and PORT respectively. Median dwell time was slightly longer for PORT (160 days) than PICC (112 days). Amongst evaluable patients (68/70), there were more complications observed in patients with PICC lines than with PORTs (47% v 12%; p = 0.001). A higher number of PICC lines were removed prematurely before treatment completion than PORTs (26% v 3%). Four patients needed PICC removal and anticoagulation due to catheter related thrombosis whereas none in PORT arm developed thrombosis. Catheter related infection requiring systemic antibiotics occurred in 1 patient in each group. Conclusion(s): PORT catheters are associated with significantly lower complication rate as compared to PICC in patients with non-haematological cancers receiving chemotherapy.

Background: Chronic indwelling central venous catheters (CVC) are being used increasingly to enable delivery of intravenous chemotherapy. Prospective randomised data comparing different types of CVC is lacking. Aim : To compare the safety of PICC vs PORT used to deliver chemotherapy in patients (PTS) with non-haematological malignancies. Method(s): We conducted a prospective multicentre randomised (1:1) clinical trial comparing a Groshong* PICC to a single chamber subcutaneously implanted port device (infusaport*, vitalcath*, powerport*). Data was collected every 3 wks from CVC insertion date. The primary endpoint of the study was the major complication rate. Secondary endpoints included CVC dwell-time, total complication rate, time to insertion of CVC and quality of life. Result(s): 68 pts from 3 centres were randomised between Dec 2004 - Jan 2010. Data has been analysed from 63 pts (32 male and 31 female; 32 PICC and 31 PORT). One pt from each arm withdrew consent prior to CVC insertion. Colon cancer was the most frequent diagnosis (61% PICC and 71% PORT). Most common indication for CVC insertion was prolonged (> 24 hours) chemotherapy infusion (75% PICC and 74% PORT). There were no complications related to the insertion procedures. Median time to insertion of CVC from randomisation was 8 days in PICC (range 1 - 28 days) and 12 days in PORT arm (range 4 - 24 days). Median dwell-time was longer for PORT (160 days) than PICC (115 days). The overall complication rate was higher in the PICC arm (45%vs 10%). Major complications occurred in 8 pts (26%) with PICC and only 1 (3%) with PORT. Of these, 4 pts in the PICC arm developed CVC thrombosis (3 within 12 wks of insertion) and another 4 pts required PICC removal due to blockage or dislodgement. The only major PORT complication was a twisted chamber. No patients in the PORT arm developed thrombosis. None of the patients had catheter related major infection requiring systemic antibiotics. Conclusion(s): PORT catheters a

Item does not contain fulltext, PURPOSE: Panitumumab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS) in chemotherapy-refractory metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone after failure of initial treatment for mCRC by tumor KRAS status. PATIENTS AND METHODS: Patients with mCRC, one prior chemotherapy regimen for mCRC, Eastern Cooperative Oncology Group performance status 0 to 2, and available tumor tissue for biomarker testing were randomly assigned 1:1 to panitumumab 6.0 mg/kg plus FOLFIRI versus FOLFIRI every 2 weeks. The coprimary end points of PFS and overall survival (OS) were independently tested and prospectively analyzed by KRAS status. RESULTS: From June 2006 to March 2008, 1,186 patients were randomly assigned 1:1 and received treatment. KRAS status was available for 91% of patients: 597 (55%) with wild-type (WT) KRAS tumors, and 486 (45%) with mutant (MT) KRAS tumors. In the WT KRAS subpopulation, when panitumumab was added to chemotherapy, a significant improvement in PFS was observed (hazard ratio [HR] = 0.73; 95% CI, 0.59 to 0.90; P = .004); median PFS was 5.9 months for panitumumab-FOLFIRI versus 3.9 months for FOLFIRI. A nonsignificant trend toward increased OS was observed; median OS was 14.5 months versus 12.5 months, respectively (HR = 0.85, 95% CI, 0.70 to 1.04; P = .12); response rate was improved to 35% versus 10% with the addition of panitumumab. In patients with MT KRAS, there was no difference in efficacy. Adverse event rates were generally comparable across arms with the exception of known toxicities associated with anti-EGFR therapy. CONCLUSION: Panitumumab plus FOLFIRI significantly improved PFS and is well-tolerated as second-line treatment in patients with WT KRAS mCRC.

Sentinel node biopsy (SNB) in primary breast cancer has been taken-up widely to avoid the morbidity attributable to axillary node clearance (ANC). Currently many issues surrounding SNB are undecided. This review summarises why some form of axillary surgery is required and presents data on all aspects of SNB including methodology, clinical results and problems that may delay the introduction of SNB as best practice for all patients with primary breast cancer. There is no long or medium term data relating to the consequences of replacing ANC with SNB, but the mechanisms and probable magnitude of both beneficial and detrimental effects are estimated. A low level of false negative results are inherent to the technique but it is demonstrated that SNB is likely to have an only marginal (0.6%) effect on survival that would be undetectable by clinical trials. Patient sub-groups particularly likely to benefit from SNB are identified. Copyright © 2002 Elsevier Science Ireland Ltd.