Gerard Vreugdenhil

Sequential versus combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (CAIRO): a phase III randomised controlled trial

BACKGROUND The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined. Our aim was to investigate whether combination treatment is better than sequential administration of the same drugs in patients with advanced colorectal cancer. METHODS We randomly assigned 820 patients with advanced colorectal cancer to receive either first-line treatment with capecitabine, second-line irinotecan, and third-line capecitabine plus oxaliplatin (sequential treatment; n=410) or first-line treatment capecitabine plus irinotecan and second-line capecitabine plus oxaliplatin (combination treatment; n=410). The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov with the number NCT00312000. FINDINGS 17 patients (nine in the sequential treatment group, eight in the combination group) were found to be ineligible and were excluded from the analysis. 675 (84%) patients died during the study: 336 in the sequential group and 339 in the combination group. Median overall survival was 16.3 (95% CI 14.3-18.1) months for sequential treatment and 17.4 (15.2-19.2) months for combination treatment (p=0.3281). The hazard ratio for combination versus sequential treatment was 0.92 (95% CI 0.79-1.08; p=0.3281). The frequency of grade 3-4 toxicity over all lines of treatment did not differ significantly between the two groups, except for grade 3 hand-foot syndrome, which occurred more often with sequential treatment than with combination treatment (13%vs 7%; p=0.004). INTERPRETATION Combination treatment does not significantly improve overall survival compared with the sequential use of cytotoxic drugs in advanced colorectal cancer. Thus sequential treatment remains a valid option for patients with advanced colorectal cancer.

Risk, severity and predictors of physical and psychological morbidity after axillary lymph node dissection for breast cancer

The aim of this study was to investigate the nature and severity of the arm complaints among breast cancer patients after axillary lymph node dissection (ALND) and to study the effects of this treatment-related morbidity on daily life and well-being. 400 women, who underwent ALND as part of breast cancer surgery, filled out a treatment-specific quality of life questionnaire. The mean time since ALND was 4.7 years (range 0.3-28 years). More than 20% of patients reported pain, numbness, or loss of strength and 9% reported severe oedema. None of the complaints appeared to diminish over time. Irradiation of the axilla and supraclavicular irradiation were associated with a 3.57-fold higher risk of oedema (odds ratio (OR) 3.57; 95% confidence interval (CI) 1.66-7.69) causing many patients to give up leisure activities or sport. Women who underwent irradiation of the breast or chest wall more often reported to have a sensitive scar than women who did not receive radiotherapy. Women <45 years of age had an approximately 6 times higher risk of numbness of the arm (OR 6.49; 95% CI 2.58-16.38) compared with those > or = 65 years of age; they also encountered more problems doing their household chores. The results of the present study support the introduction of less invasive techniques for the staging of the axilla, sentinel node biopsy being the most promising.

Chemotherapy-Induced Neuropathy and Its Association With Quality of Life Among 2- to 11-Year Colorectal Cancer Survivors: Results From the Population-Based PROFILES Registry

PURPOSE To gain insight into the prevalence and severity of chemotherapy-induced neuropathy and its influence on health-related quality of life (HRQOL) in a population-based sample of colorectal cancer (CRC) survivors 2 to 11 years after diagnosis. METHODS All alive individuals diagnosed with CRC between 2000 and 2009 as registered by the Dutch population-based Eindhoven Cancer Registry were eligible for participation. Eighty-three percent (n = 1,643) of patients filled out the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the EORTC QLQ Chemotherapy-Induced Peripheral Neuropathy 20. RESULTS The five neuropathy subscale-related symptoms that bothered patients with CRC the most during the past week were erectile problems (42% of men), trouble hearing (11%), trouble opening jars or bottles (11%), tingling toes/feet (10%), and trouble walking stairs or standing up (9%). Additionally, patients who received oxaliplatin more often reported tingling (29% v 8%; P = .001), numbness (17% v 5%; P = .005), and aching or burning pain (13% v 6%; P = .03) in toes/feet compared with those not treated with chemotherapy. They also more often reported tingling toes/feet (29% v 14%; P = .0127) compared with those treated with chemotherapy without oxaliplatin. Those with many neuropathy symptoms (eg, upper 10%) reported statistically significant and clinically relevant worse HRQOL scores on all EORTC QLQ-C30 subscales (all P < .01). CONCLUSION Two to 11 years after diagnosis of CRC, neuropathy-related symptoms are still reported, especially sensory symptoms in the lower extremities among those treated with oxaliplatin. Because neuropathy symptoms have a negative influence on HRQOL, these should be screened for and alleviated. Future studies should focus on prevention and relief of chemotherapy-induced neuropathy.

Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review

BackgroundThe objective of this study was to systematically review all available literature concerning chemotherapy-induced peripheral neuropathy (CIPN) and quality of life (QOL) among cancer patients.MethodsA computerized search of the literature was performed in December 2013. Articles were included if they investigated CIPN and QOL among cancer patients. Twenty-five articles were selected and were subjected to a 13-item quality checklist independently by two investigators.ResultsThe methodological quality of the majority of the selected studies was adequate to high. The included studies differed tremendously with respect to study design (19 prospective studies, 5 cross-sectional, 1 both cross-sectional and prospective), patient population (lung, colorectal, ovarian, endometrial, cervical or breast cancer, lymphoma, acute lymphoblastic leukemia, or a mixed population), number of included patients (ranging from 14 to 1643), and ways to assess CIPN (objectively, subjectively, or both). Of the 25 included studies, 11 assessed the association of CIPN on patients’ QOL. While three of these studies did not find an association between CIPN and QOL, the others concluded that more CIPN was associated with a lower QOL.Implications for cancer survivorsAlthough the included studies in this systematic review were very diverse, which impedes drawing firm conclusions on this topic, CIPN is likely to have a negative association with QOL. The variety of the studied patient populations and chemotherapeutic agents in the existing studies calls for further studies on this topic. These studies are preferably prospective in nature, include a large number of patients, and assess QOL and CIPN with validated questionnaires.

Efficacy of Itraconazole in the Prevention of Fungal Infections Among Neutropenic Patients with Hematologic Malignancies and Intensive Chemotherapy. A Double Blind, Placebo Controlled Study

We studied the efficacy and safety of itraconazole for the prevention of fungal infection in neutropenic patients given cytotoxic chemotherapy for hematologic malignancies. Patients were randomly allocated to receive either itraconazole (200 mg bd) or placebo in addition to oral amphotericin B until the patient either developed fungal infection or had completed antileukemic treatment. Forty six patients (83 neutropenic episodes) treated with itraconazole and 46 placebo treated patients (84 neutropenic episodes) were evaluable. No specific toxicity was noted. Nine fungal infections developed in the itraconazole group, of which four were histologically or microbiologically proven and 15 in the patients given placebo (eight proven) (p < 0.12). All these patients received IV amphotericin B. The incidence of Candida albicans infections tended to be lower in the itraconazole group, but overall, there was no measurable improvement in the prevention of fungal infections and mortality by itraconazole.

Resistance training in cancer survivors: a systematic review.

This systematic review summarizes the research of previous studies that used resistance training in the post-treatment phase of cancer patients with a focus on methodological quality, training methods and physical outcome measures. We found twenty-four studies (10 RCTs, 4 controlled clinical trials and 10 uncontrolled trials) that met all inclusion criteria. The studies were of moderate methodological quality. The majority of studies involved breast cancer patients (54%), followed by prostate cancer patients (13%). Most studies used a combination of resistance and aerobic training, which was mostly supervised. Resistance training involved large muscle groups, with 1-3 sets of 8-12 repetitions. The duration of the resistance training programs varied from 3-24 weeks, with a training frequency of 1-5 sessions per week. The training intensity ranged from 25% to 85% of the one-repetition maximum. Overall, positive training effects were observed for cardiopulmonary and muscle function, with significant increases in peak oxygen uptake (range: 6-39%), and in the one-repetition maximum (range: 11-110%). In general, there were no effects of training on body composition, endocrine and immune function, and haematological variables. No adverse effects of the resistance training were reported. Based upon these results, we recommend to incorporate resistance training in cancer rehabilitation programmes.

Comorbidity has negligible impact on treatment and complications but influences survival in breast cancer patients

In the present study, we investigated whether age and serious comorbid conditions influence treatment decisions, complications and survival in breast cancer patients. The Eindhoven Cancer Registry records patient, tumour and therapy characteristics of all patients diagnosed with cancer in the southern part of the Netherlands. Additional information on severity of comorbidity and serious complications was collected for a random sample of 527 breast cancer patients (aged 40 years and older). More than 70% of the patients ⩾80 exhibited high severity of comorbidity compared to 6% of those aged 40–49 years. Treatment was not influenced by severity of comorbidity. Less than 30% of the breast cancer patients had complications after diagnosis. The number of complications was not related to age or severity of comorbidity. The hazard ratio (HR) of dying for patients with low/moderate severity of comorbidity was 2.4 for those aged 40–69 years and 1.6 for those aged ⩾70 years, after adjustment for age, nodal status and treatment. For patients with high severity of comorbidity, the risk of dying was almost three times higher. Older breast cancer patients with serious comorbidity were not treated differently and did not have more complications compared to those without comorbidity, but they exhibited a worse prognosis.

New opportunities for drug outcomes research in cancer patients: The linkage of the Eindhoven Cancer Registry and the PHARMO Record Linkage System

BACKGROUND Insight into co-morbidity and treatment effects is pivotal to improve quality of care for cancer patients. OBJECTIVES To determine whether linkage of the Eindhoven Cancer Registry (ECR) and the PHARMO Record Linkage System (RLS) was technically feasible and to assess which patient-centric data would result from this linkage. METHODS The ECR records data on tumour stage and primary treatment of all newly diagnosed cancer patients in the southeastern Netherlands including co-morbidity at diagnosis, whereas the PHARMO RLS includes data from multiple linked observational databases such as data on drug utilisation (for both in- and out-patients, including chemotherapy), hospitalisations and clinical laboratory measurements. All patients who lived or had been living in the overlapping area served by the ECR and the PHARMO RLS during 1998-2006 were selected for linkage which was performed with probabilistic medical record linkage. RESULTS The linkage resulted in an ECR-PHARMO cohort of 40,004 cancer patients with a total of 42,767 primary tumours. The cancer patients in the linked ECR-PHARMO cohort were representatives for the cancer patients included in the total ECR during 1998-2006. Cancer patients included in the cohorts had a mean history of 5 years and a mean follow-up ranging from 2 to more than 4 years (dependent on the survival rate of the specific cancer type). CONCLUSIONS Linkage of ECR and the PHARMO RLS creates the possibility to study patient-centric drug utilisation, health resources utilisation and their costs, in addition to the effectiveness and safety of pharmaceuticals in routine daily practice in cancer patients.

Quality of life among long-term non-Hodgkin lymphoma survivors : A population-based study

The objective of this population‐based study was to document the long‐term effects (5–15 years postdiagnosis) of non‐Hodgkin lymphoma and its treatment on health‐related quality of life (HRQL) and social problems.

Long-term cancer survivors experience work changes after diagnosis: Results of a population-based study.

Background: Although cancer survivorship is increasing with improved diagnosis and treatments, few studies have explored employment changes and the factors related to this change among cancer survivors. Therefore, we aim to explore the prevalence of employment problems in long‐term cancer survivors. In addition, we explored what patient or tumour characteristics predicted employment changes.