Variations in the definition and perceived importance of positive resection margins in patients with colorectal cancer - an EYSAC international survey.

INTRODUCTION: Microscopically positive resection margins (R1) are associated with poorer outcomes in patients with colorectal cancer. However, different definitions of R1 margins exist. It is unclear to what extent the definitions used in everyday clinical practice differ within and between nations. This study sought to investigate variations in the definition of R1 margins in colorectal cancer and the importance of margin status in clinical decision-making. MATERIALS AND METHODS: A 14-point survey was developed by members of The European Society of Surgical Oncology (ESSO) Youngs Surgeons and Alumni Club (EYSAC) Research Academy targeting all members of the multidisciplinary team (MDT) treating patients with colorectal cancer. The survey was distributed on social media, in ESSO's monthly newsletter and via national societies. RESULTS: In total, 137 responses were received. Most respondents were from Europe (89.7%), with the majority from Denmark (56.9%). Less than 2/3 of respondents defined R1 margins as the presence of viable cancer cells ≤1 mm of the margin. Only 60% reported that subdivisions of R1 margins (primary tumour vs tumour deposit vs metastatic lymph node) are routinely available. More than 20% of respondents reported that pathology reports are not routinely reviewed at MDT meetings. Less than half of respondents considered margin status in decision-making for type and duration of adjuvant chemotherapy in Stage III colon cancer. CONCLUSION: The definitions and perceived clinical importance of microscopically positive margins in patients with colorectal cancer appear to vary. Adoption of an international dataset for pathology reporting may help to standardise current practices.

Differences in adjuvant chemotherapy and oncological outcomes according to margin status in patients with stage III colon cancer.

BACKGROUND: Microscopically positive margins to lymph node metastases (R1LNM) are associated with poorer oncological outcomes in patients with Stage 3 colon cancer. These poorer outcomes were seen despite a greater proportion of these patients receiving adjuvant chemotherapy when compared to those with microscopically negative (R0) margins. We sought to determine if differences in the type or duration of adjuvant chemotherapy could account for the differences in outcomes seen between patients with R0 and R1LNM margins. METHODS: A multicentre retrospective study including patients undergoing surgery for Stage 3 colon cancer between 2016-2019 at specialist centres. Patients were stratified according to margins status (R0 vs R1LNM). Type/duration of chemotherapy and oncological outcomes were compared between groups. RESULTS: 718 patients were included, of whom 100 had R1LNM margins (13.1%). Patients with R1LNM margins had significantly poorer 3-year distant metastases-free (R0 78.2% (95% CI 74.5-81.3) versus R1LNM 58.8% (95% CI 47.2-68.6), p < 0.001) and disease specific survival (R0 88.3% (95% CI 85.2-90.9) versus R1LNM 78.5% (95% CI 68.0-85.8), p < 0.001) when compared to those with R0 margins. No differences were noted in the proportion of patients who completed long-course chemotherapy or were treated with oxaliplatin-based combinations between the R1LNM and R0 groups. Differences in outcomes between R0 and R1LNM groups persisted even when only those patients who completed long-course chemotherapy were compared. DISCUSSION: Differences in adjuvant chemotherapy do not appear to account for the poorer oncological outcomes seen in patients with R1LNM margins after surgery for Stage 3 colon cancer. This suggests that adjuvant chemotherapy may be less effective in this patient group. Further studies to elucidate a potential biological basis for this difference are warranted.

Implementation and clinical benefit of DPYD genotyping in a Danish cancer population.

BACKGROUND: In 2020, the European Medicines Agency recommended testing patients for dihydropyrimidine dehydrogenase (DPD) deficiency before systemic treatment with fluoropyrimidines (FP). DPD activity testing identifies patients at elevated risk of severe FP-related toxicity (FP-TOX). The two most used methods for DPD testing are DPYD genotyping and DPD phenotyping (plasma uracil concentration). The primary objective of this study was to compare the overall frequency of overall grade ≥3 FP-TOX before and after the implementation of DPYD genotyping. PATIENTS AND METHODS: Two hundred thirty Danish, primarily gastrointestinal cancer patients, were DPYD-genotyped before their first dose of FP, and blood was sampled for post hoc assessment of P-uracil. The initial dose was reduced for variant carriers. Grade ≥3 FP-TOX was registered after the first three treatment cycles of FP. The frequency of toxicity was compared to a historical cohort of 492 patients with post hoc determined DPYD genotype from a biobank. RESULTS: The frequency of overall grade ≥3 FP-TOX was 27% in the DPYD genotype-guided group compared to 24% in the historical cohort. In DPYD variant carriers, DPYD genotyping reduced the frequency of FP-related hospitalization from 19% to 0%. In the control group, 4.8% of DPYD variant carriers died due to FP-TOX compared to 0% in the group receiving DPYD genotype-guided dosing of FP. In the intervention group, wild-type patients with uracil ≥16 ng/ml had a higher frequency of FP-TOX than wild-type patients with uracil <16 ng/ml (55% versus 28%). CONCLUSIONS: We found no population-level benefit of DPYD genotyping when comparing the risk of grade ≥3 FP-TOX before and after clinical implementation. We observed no deaths or FP-related hospitalizations in patients whose FP treatment was guided by a variant DPYD genotype. The use of DPD phenotyping may add valuable information in DPYD wild-type patients.

Effects of high-intensity exercise training on physical fitness, quality of life and treatment outcomes after oesophagectomy for cancer of the gastro-oesophageal junction: PRESET pilot study.

BACKGROUND: Treatment for cancer of the gastro-oesophageal junction (GOJ) can result in considerable and persistent impairment of physical fitness and health-related quality of life (HRQoL). This controlled follow-up study investigated the feasibility and safety of postoperative exercise training. METHODS: Patients with stage I-III GOJ cancer were allocated to 12 weeks of postoperative concurrent aerobic and resistance training (exercise group) or usual care (control group). Changes in cardiorespiratory fitness, muscle strength and HRQoL were evaluated. Adherence to adjuvant chemotherapy, hospitalizations and 1-year overall survival were recorded to assess safety. RESULTS: Some 49 patients were studied. The exercise group attended a mean of 69 per cent of all prescribed sessions. After exercise, muscle strength and cardiorespiratory fitness were increased and returned to pretreatment levels. At 1-year follow-up, the exercise group had improved HRQoL (+13·5 points, 95 per cent c.i. 2·2 to 24·9), with no change in the control group (+3·7 points, -5·9 to 13·4), but there was no difference between the groups at this time point (+9·8 points, -5·1 to 24·8). Exercise was safe, with no differences in patients receiving adjuvant chemotherapy (14 of 16 versus 16 of 19; relative risk (RR) 1·04, 95 per cent c.i. 0·74 to 1·44), relative dose intensity of adjuvant chemotherapy (mean 57 versus 63 per cent; P = 0·479), hospitalization (7 of 19 versus 6 of 23; RR 1·41, 0·57 to 3·49) or 1-year overall survival (80 versus 79 per cent; P = 0·839) for exercise and usual care respectively. CONCLUSION: Exercise in the postoperative period is safe and may have the potential to improve physical fitness in patients with GOJ cancer. No differences in prognostic endpoints or HRQoL were observed. Registration number: NCT02722785 ( https://www.clinicaltrials.gov).

ANTECEDENTES: El tratamiento del cáncer de la unión gastroesofágica (gastroesophageal junction, GEJ) puede determinar un deterioro considerable y persistente de la condición física y de la calidad relacionada con la salud (health-related quality of life, HRQoL). El objetivo de este estudio controlado de seguimiento fue investigar la factibilidad y seguridad del entrenamiento físico postoperatorio. MÉTODOS: Pacientes con cáncer de GEJ en estadio I-III fueron asignados a 12 semanas de entrenamiento postoperatorio simultáneo aeróbico y de resistencia o a cuidados médicos habituales. Se evaluaron los cambios en el estado cardiorrespiratoria, fuerza muscular y HRQoL. Se recogieron datos de la adherencia a la quimioterapia adyuvante, hospitalizaciones y supervivencia global a 1 año para evaluar la seguridad. RESULTADOS: Se estudiaron un total de 49 pacientes. El grupo con ejercicio asistió al 69% de todas las sesiones planificadas. Después del ejercicio, la fuerza muscular y el estado cardiorrespiratorio aumentaron y volvieron a los niveles previos al tratamiento. Si bien al año de seguimiento, el grupo con ejercicio presentó una mejoría de la HRQoL (+13,5 puntos (i.c. del 95% 2,2 a 24,9)), sin cambios en el grupo con atención médica habitual (+3,7 puntos (i.c. del 95% −5,9 a 13,4)), no hubo diferencias entre los grupos en ese momento (+9,8 puntos (i.c. del 95% −5,1 a 24,8)). El ejercicio fue seguro, sin diferencias entre el ejercicio o la atención médica habitual en pacientes que recibían quimioterapia adyuvante 87,5% versus 84,2% (RR 1,04 (i.c. del 95% 0,74 a 1,44)), intensidad relativa de la dosis de quimioterapia adyuvante 56,8% versus 63,3% (P = 0,479), hospitalizaciones 36,8% versus 26,1% (RR 1,41 (i.c. del 95% 0,57 a 3,49)) o supervivencia global a 1 año 80,0% versus 79,3% (P = 0,839). CONCLUSIÓN: El ejercicio en el periodo postoperatorio es seguro y puede tener potencial para mejorar la condición física en pacientes con cáncer de GEJ. No se observaron diferencias en los resultados pronósticos o en la HRQoL.

Early changes in tests of peripheral nerve function during oxaliplatin treatment and their correlation with chemotherapy-induced polyneuropathy symptoms and signs.

BACKGROUND AND PURPOSE: Assessment of the severity of chronic peripheral neuropathy during oxaliplatin treatment is based on symptoms. Efforts to adjust the total dose of oxaliplatin to prevent severe neuropathy can be complicated by the worsening of neuropathy symptoms following treatment. Objective measures of the structure and function of peripheral nerves during early phases of treatment may aid in determining the optimal oxaliplatin dose in individual patients. Intraepidermal nerve fibre density (IENFD) has been suggested as an early marker of peripheral neuropathy. METHODS: Sixty patients were examined before treatment and following 25% and 50% of the total planned oxaliplatin dose. Fifty-five of them were also examined at completion of chemotherapy and 6 months later. IENFD in skin biopsies from the distal leg, nerve conduction studies and quantitative sensory testing at the dorsum of the foot were performed. Forty-six healthy subjects were examined at baseline and after 6 and 52 weeks for comparison. RESULTS: Intraepidermal nerve fibre density was not reduced during treatment. Sural nerve amplitude and conduction velocity, vibration detection thresholds, mechanical detection threshold and cold detection threshold were significantly reduced during treatment. Compared to reference values and spontaneous changes in healthy subjects, the largest proportions of patients with deterioration were found for vibration detection thresholds followed by nerve conduction studies, mechanical detection threshold, cold detection threshold and IENFD. CONCLUSIONS: Significant changes were most pronounced for measures of large nerve fibre function, especially vibration sensation. Skin biopsies do not seem to provide a clinically relevant objective measure of peripheral nerve deterioration during oxaliplatin treatment.

Professional burnout in European young oncologists: results of the European Society for Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey.

BACKGROUND: Burnout in health care professionals could have serious negative consequences on quality of patient care, professional satisfaction and personal life. Our aim was to investigate the burnout prevalence, work and lifestyle factors potentially affecting burnout amongst European oncologists ≤40 (YOs). METHODS: A survey was conducted using the validated Maslach Burnout Inventory (MBI) and additional questions exploring work/lifestyle factors. Statistical analyses were carried out to identify factors associated with burnout. RESULTS: Total of 737 surveys (all ages) were collected from 41 European countries. Countries were divided into six regions. Results from 595 (81%) YOs were included (81% medical oncologists; 52% trainees, 62% women). Seventy-one percent of YOs showed evidence of burnout (burnout subdomains: depersonalization 50%; emotional exhaustion 45; low accomplishment 35%). Twenty-two percent requested support for burnout during training and 74% reported no hospital access to support services. Burnout rates were significantly different across Europe (P < 0.0001). Burnout was highest in central European (84%) and lowest in Northern Europe (52%). Depersonalization scores were higher in men compared with women (60% versus 45% P = 0.0001) and low accomplishment was highest in the 26-30 age group (P < 0.01). In multivariable linear regression analyses, European region, work/life balance, access to support services, living alone and inadequate vacation time remained independent burnout factors (P < 0.05). CONCLUSIONS: This is the largest burnout survey in European Young Oncologists. Burnout is common amongst YOs and rates vary across Europe. Achieving a good work/life balance, access to support services and adequate vacation time may reduce burnout levels. Raising awareness, support and interventional research are needed.

Characterization and diagnostic evaluation of chronic polyneuropathies induced by oxaliplatin and docetaxel comparing skin biopsy to quantitative sensory testing and nerve conduction studies.

BACKGROUND AND PURPOSE: Chemotherapy-induced peripheral neuropathy negatively affects the quality of life for many patients treated with oxaliplatin or docetaxel for gastrointestinal cancer or breast cancer. Symptoms can persist long after treatment and often include neuropathic pain. Our objective was to characterize the neuropathies with regard to symptoms, neurological signs and objective evidence of damage to the structure and function of the peripheral nerves. Furthermore, the diagnostic values of skin biopsy, quantitative sensory testing (QST) and nerve conduction studies (NCS) were compared. METHODS: Patients complaining of neuropathy symptoms at least 3 months after completion of treatment with oxaliplatin (n = 20) or docetaxel (n = 20) were recruited from the Department of Oncology or using hospital records. Neuropathy scores were determined along with the intraepidermal nerve fibre density in skin biopsies from the proximal and distal parts of the leg, QST and NCS. RESULTS: Clinically only sensory functions were affected. In general, neuropathy scores were higher in the oxaliplatin-treated group. Both sensory and motor fibres were affected in the NCS, showing predominantly signs of axonal damage. Mechanical detection threshold was most often affected in the QST. NCS, QTS and skin biopsy were abnormal in 11, 13 and 17 and 7, 11 and 15 of the oxaliplatin-treated patients and docetaxel-treated patients, respectively. CONCLUSIONS: Chemotherapy-induced peripheral neuropathy after oxaliplatin or docetaxel treatment is a clinically sensory, axonal neuropathy affecting only small nerve fibres in some patients. NCS are often normal, whereas QST and skin biopsy have a higher diagnostic sensitivity.

Age-dependent improvement in median and long-term survival in unselected population-based Nordic registries of patients with synchronous metastatic colorectal cancer.

BACKGROUND: In metastatic colorectal cancer (mCRC) trials, median survival has increased from 6 months to above 20 months during the previous decades. Uncertainty exists in how this survival improvement has translated to the general mCRC population. PATIENTS AND METHODS: Survival data from patients with synchronous mCRC were collected from the Norwegian (1980-2008), Swedish (1996-2008) and Danish (2001-09) cancer registries. RESULTS: A total of 29 628 patients were identified. From 1980-1985 to 2006-2008, median survival increased from 5 to 10 months for Norwegian patients. Three-year survival increased from 7% to 21% and 5-year survival from 4% to 9%. For patients <60 years, median survival was doubled to 16 months, 3-year survival increased fourfold up to 28% and 5-year survival threefold up to 14%. Similar improvements were seen in Sweden and Denmark. In all countries, the improved outcome was seen especially for younger patients and much less for patients >75 years of age. CONCLUSION: An increase in median and long-term survival over time was found in unselected population-based registries of patients with synchronous mCRC. The improved outcome in survival was especially seen in younger patients, raising concerns over our ability to adapt available treatment options for elderly patients.

Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone.

BACKGROUND: Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored. METHODS: A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n=781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively. RESULTS: Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04-0.85, P=0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10-0.86, P=0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10-4.49, P=0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P<0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity. CONCLUSION: Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC.

Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer.

BACKGROUND: The aim was to evaluate the association between plasma tissue inhibitor of metalloproteinase-1 (TIMP-1) and serum carcinoembryonic antigen (CEA) levels and outcome in patients with metastatic colorectal cancer (mCRC) receiving XELOX (combination chemotherapy with capecitabine and oxaliplatin) as first-line treatment. PATIENTS AND METHODS: One hundred and twenty patients were included. Blood samples were collected before treatment and 3 weeks later before the next treatment cycle. Plasma TIMP-1 and serum CEA levels were correlated to treatment outcome. RESULTS: No significant associations between baseline TIMP-1 or CEA levels and best response to treatment or progression-free survival (PFS) could be demonstrated. In contrast, high baseline plasma TIMP-1 levels were associated with poor overall survival (OS), P = 0.008, hazard ratio (HR) = 1.80 [95% confidence interval (CI): 1.17-2.78]. Furthermore, increase in TIMP-1 levels from baseline to immediately before the second cycle of chemotherapy had a significant negative effect on survival (P = 0.03, HR = 1.30, 95% CI: 1.02-1.65) while a decrease in TIMP-1 was significantly associated with a higher objective response rate (P = 0.03). CONCLUSIONS: Both high baseline and subsequent increase in TIMP-1 levels were associated with shorter OS in patients with mCRC receiving XELOX as first-line treatment, whereas baseline TIMP-1 levels were not associated with response or PFS following XELOX treatment.

A randomized study comparing short-time infusion of oxaliplatin in combination with capecitabine XELOX(30) and chronomodulated XELOX(30) as first-line therapy in patients with advanced colorectal cancer.

BACKGROUND: Chronotherapy is one of the several approaches to increase efficacy and reduce toxicity of chemotherapy. In a phase II study in the second-line in patients with metastatic colorectal cancer (mCRC), we found that chronomodulated XELOX (XELOX(30Chron)) was a well-tolerated regimen with potentially reduced toxicity. PATIENTS AND METHODS: One hundred and forty-one patients with unresectable mCRC were enrolled in a randomized study comparing standard XELOX (XELOX(30)), arm A, and XELOX(30Chron), arm B-both with short-time infusion of oxaliplatin-with the primary aim of reducing overall toxicity. RESULTS: Overall toxicity grade 2-4 was 90% versus 85%, P = 0.47 and grade 3-4 was 31% versus 37%, P = 0.6 in arm A and B, respectively. We found no significant differences in median overall survival (17.6 versus 15.5 months; P = 0.068) and median progression-free survival (8.9 versus 8.8 months; P = 0.7). The incidence of grade 3 neuropathy was 16% in arm A and 19% in arm B (P = 0.7) after a cumulative dose of oxaliplatin of 1000 mg/m(2). CONCLUSION: XELOX(30Chron) does not reduce toxicity or improve efficacy. A 30-min infusion of oxaliplatin is safe and does not increase the severity of chronic neuropathy.

A window of opportunity phase II study of enzastaurin in chemonaive patients with asymptomatic metastatic colorectal cancer.

BACKGROUND: Preclinically, protein kinase C and AKT activation can be inhibited by enzastaurin and reduce tumor growth of colorectal cancer cells. In asymptomatic patients with metastatic colorectal cancer (mCRC), enzastaurin activity was evaluated by measuring the 6-month progression-free survival (PFS) rate in a window study design. PATIENTS AND METHODS: Chemonaive patients with asymptomatic mCRC who did not require immediate chemotherapy-induced tumor reduction received a 400-mg thrice daily loading dose of enzastaurin on day 1 of cycle 1, followed by 500 mg once daily for the remaining 28-day cycles. Progression was assessed on the basis of radiographic imaging, rise in carcinoembryonic antigen or lactate dehydrogenase (LDH) levels or by appearance of clinical symptoms. RESULTS: Twenty-eight patients received daily enzastaurin. The 6-month PFS rate was 28% [95% confidence interval (CI) 13%-45%] and median PFS was 1.9 months (95% CI 1.8-4.5 months). Twelve (43%) patients had stable disease with a median duration of 6.1 months. The survival rate at 20 months was 77% (95% CI 47%-92%). No grade 4 toxicity was reported and grade 3 toxic effects were observed in three patients with one patient showing probable drug-related elevation of liver transaminases. CONCLUSION: The window design in asymptomatic patients with mCRC can be safely applied to assess the activity and safety of novel cytostatic agents like enzastaurin.

Biweekly cetuximab and irinotecan as third-line therapy in patients with advanced colorectal cancer after failure to irinotecan, oxaliplatin and 5-fluorouracil.

BACKGROUND: Standard weekly cetuximab and irinotecan (CetIri) is an effective regimen in heavily pretreated patients with advanced colorectal cancer (ACRC). Inspired by a pharmacokinetic study demonstrating no differences between weekly and biweekly cetuximab, we present the results of 74 consecutive patients treated with biweekly CetIri. METHODS: Biweekly CetIri schedule: cetuximab 500 mg/m(2), first course was given as a 120-min infusion followed 1 h later by irinotecan 180 mg/m(2) as a 30-min infusion. Subsequent courses of cetuximab were given in 60 min, immediately followed by irinotecan-resulting in an overall treatment time of 90 min. RESULTS: All patients had ACRC resistant to 5-fluorouracil and irinotecan and 95% to oxaliplatin. Median age was 63 years, median performance status was 0. Median duration of therapy was 4.3 months. Response rate was 25%. Median progression-free survival and overall survival were 5.4 months and 8.9 months, respectively, comparable to own historical controls receiving weekly CetIri. Grade 3-4 toxicity was rare (skin 7%, nail 3%, diarrhoea 10%, fatigue 3%, neutropenia 9%). One patient experienced severe allergic reaction. CONCLUSION: Salvage therapy with simplified biweekly CetIri is a convenient, effective and well-tolerated regimen in heavily pretreated patients with ACRC. A confirmatory phase II study is ongoing.

Chronomodulated capecitabine in combination with short-time oxaliplatin: a Nordic phase II study of second-line therapy in patients with metastatic colorectal cancer after failure to irinotecan and 5-flourouracil.

BACKGROUND: Oxaliplatin in combination with capecitabine prolongs survival in patients with metastatic colorectal cancer (mCRC). Chronomodulation might reduce toxicity and improve efficacy. PATIENTS AND METHODS: A phase II study examining chronomodulated XELOX(30) (XELOX(30chron)): oxaliplatin: 130 mg/m(2) on day 1, as a 30-min infusion between 1 and 3 p.m. Capecitabine: total daily dose of 2000 mg/m(2), 20% of the dose between 7 and 9 a.m. and 80% of the dose between 6 and 8 p.m. in patients with mCRC resistant to irinotecan. Seventy-one patients were enrolled. Response rate was 18%; median progression-free survival 5.1 months and median overall survival (OS) 10.2 months. Platelet count and performance status were significantly correlated to OS in multivariate analyses. Neurotoxicity grade 2 and 3 was seen in 25% and 2% of patients, respectively, other grade 3 toxic effects were as follows: nausea 6%, vomiting 3%, diarrhoea 12% (3% experienced grade 4) and palmoplantart erytem 9%. CONCLUSION: XELOX(30chron) is a convenient second-line regimen with efficacy and safety profile similar to other oxaliplatin schedules. To further investigate chronomodulated XELOX, we have started a Nordic randomised phase II study comparing XELOX(30) and XELOX(30chron) as first-line therapy in patients with mCRC.

Current role of antibody therapy in patients with metastatic colorectal cancer.

In less than 10 years, the number and importance of non-surgical treatment modalities in patients with colorectal cancer (CRC) have increased dramatically, both in the adjuvant and the advanced settings. However, despite the improvement of cytotoxic therapy in CRC, many patients still develop progressive disease and unfortunately in patients with disease resistant to 5-fluorouracil/folinic acid, irinotecan and oxaliplatin, no effective cytotoxic therapy is known. The rapidly expanding knowledge in tumor biology has encouraged optimism for the possibility to find and target tumor-specific mechanisms and thereby increase both efficacy and tolerance. A great number of 'targeted drugs' are being tested in clinical trials and some of these new drugs, like bevacizumab, cetuximab and panitumumab, are available for routine use in health care. These new targeted drugs will expand the therapeutic arsenal in CRC to a great extent, but they will also add to the complexity of treatment of CRC. In this review, we summarize the current status of antibody therapy in patients with CRC.

Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil.

BACKGROUND: The efficacy of oxaliplatin combined with capecitabine (XELOX) as second-line therapy in patients with advanced colorectal cancer (ACRC) resistant to irinotecan is not well established. Oxaliplatin induces acute, cold-induced neuropathy in most patients. The incidence is claimed to be infusion rate-dependent and therefore a 2-h infusion is recommended. PATIENTS AND METHODS: For practical and economic reasons, but also for patient's convenience, we performed a phase II study to examine XELOX30 (capecitabine 1000 mg/m2 orally twice daily on days 1-14 and oxaliplatin 130 mg/m2 as a 30 min infusion on day 1) in patients with ACRC resistant to irinotecan. In addition the pharmacokinetics of oxaliplatin was studied. RESULTS: From November 2002 to September 2003, 70 patients with ACRC were treated with XELOX30. Median age was 62 (range 33-74 years) years and median performance status was 1 (range 0-2). The median number of courses was four (range 1-12) and median cumulative dose of oxaliplatin was 530 (range 125-1560) mg/m2. The response rate was 17% (95% CI 10-23), median time to progression (TTP) was 5.4 months (95% CI 4.6-6.4) and median survival 9.5 months (95% CI 8.5-11.2). White blood cell count (WBC) and performance status were significantly correlated to TTP. Neurotoxicity was moderate: grade 1 56%, grade 2 17% and grade 3 6%. Other grade 3 toxicities were nausea/vomiting 9%, diarrhoea 14% and PPE 8%. The maximum blood concentration and total body clearance of oxaliplatin was higher than previously reported in studies examining 2-h infusions, but the volume of distribution and terminal half-life was in close agreement with previous results. CONCLUSION: XELOX30 is a very convenient second-line regimen in ACRC with an activity and safety profile similar to other oxaliplatin schedules.