• Capecitabine, bevacizumab, and mitomycin in first-line treatment of metastatic colorectal cancer: results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study.

      Tebbutt, Niall C; Wilson, Kate; Gebski, Val; Cummins, Michelle M; Zannino, Diana; Van Hazel, Guy A; Robinson, Bridget; Broad, Adam; Ganju, Vinod; Ackland, Stephen P; et al. (2010-07-01)
      PURPOSE: To determine whether adding bevacizumab, with or without mitomycin, to capecitabine monotherapy improves progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC) in an open-label, three-arm randomized trial. PATIENTS AND METHODS: Overall, 471 patients in Australia, New Zealand, and the United Kingdom with previously untreated, unresectable mCRC were randomly assigned to the following: capecitabine; capecitabine plus bevacizumab (CB); or capecitabine, bevacizumab, and mitomycin (CBM). We compared CB with capecitabine and CBM with capecitabine for progression-free survival (PFS). Secondary end points included overall survival (OS), toxicity, response rate (RR), and quality of life (QOL). RESULTS: Median PFS was 5.7 months for capecitabine, 8.5 months for CB, and 8.4 months for CBM (capecitabine v CB: hazard ratio [HR], 0.63; 95% CI, 0.50 to 0.79; P < .001; C v CBM: HR, 0.59; 95% CI, 0.47 to 0.75; P < .001). After a median follow-up of 31 months, median OS was 18.9 months for capecitabine and was 16.4 months for CBM; these data were not significantly different. Toxicity rates were acceptable, and all treatment regimens well tolerated. Bevacizumab toxicities were similar to those in previous studies. Measures of overall QOL were similar in all groups. CONCLUSION: Adding bevacizumab to capecitabine, with or without mitomycin, significantly improves PFS without major additional toxicity or impairment of QOL.
    • Clinical neurological outcome and quality of life among patients with limited small-cell cancer treated with two different doses of prophylactic cranial irradiation in the intergroup phase III trial (PCI99-01, EORTC 22003-08004, RTOG 0212 and IFCT 99-01).

      Le Péchoux, C; Laplanche, A; Faivre-Finn, Corinne; Ciuleanu, T; Wanders, R; Lerouge, D; Keus, R; Hatton, M; Videtic, G M; Senan, S; et al. (2011-05)
      We recently published the results of the PCI99 randomised trial comparing the effect of a prophylactic cranial irradiation (PCI) at 25 or 36 Gy on the incidence of brain metastases (BM) in 720 patients with limited small-cell lung cancer (SCLC). As concerns about neurotoxicity were a major issue surrounding PCI, we report here midterm and long-term repeated evaluation of neurocognitive functions and quality of life (QoL).
    • Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial.

      Warde, P; Mason, M; Ding, K; Kirkbride, P; Brundage, M; Cowan, Richard A; Gospodarowicz, M; Sanders, K; Kostashuk, E; Swanson, G; et al. (2011-12-17)
      Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer.
    • Comparison of patient-reported late treatment toxicity (LENT-SOMA) with quality of life (EORTC QLQ-C30 and QLQ-H&N35) assessment after head and neck radiotherapy.

      Ho, Kean F; Farnell, Damian J J; Routledge, Jacqueline A; Burns, Meriel P; Sykes, Andrew J; Slevin, Nicholas J; Davidson, Susan E; Academic Radiation Oncology, University of Manchester, The Christie NHS Foundation Trust, Manchester, UK. (2010-06-14)
      PURPOSE: The patient's role in toxicity reporting is increasingly acknowledged but requires the adaptation and validation of toxicity reporting instruments for patient use as most toxicity scales are designed for physician use. Recording of radiotherapy related late toxicity is important and needs to be improved. A patient-scored symptom questionnaire of late treatment effects using LENT-SOMA was compared with a recognised quality of life tool (EORTC QLQ-C30/H&N35). MATERIALS/METHODS: LENT-SOMA and EORTC QLQ-C30 patient questionnaires were prospectively completed by 220 head and neck cancer patients over 3years and 72 completed EORTC QLQ-H&N35 questionnaires at 2years post-radiotherapy. RESULTS: Endpoints common to both questionnaires (pain, swallowing, dental pain, dry mouth, opening mouth, analgesics) were matched. Spearman rank correlation coefficients with rho>0.6 (P<0.001) were obtained for all "matched" scales except for analgesics scale, rho=0.267 (P<0.05). There was good agreement between LENT-SOMA and EORTC QLQ-H&N35 except for analgesic endpoints. Global quality of life scores correlated negatively with average LENT-SOMA scores (P<0.001). Significant differences in average LENT-SOMA scores between treatment modalities were found. The LENT-SOMA questionnaire has demonstrated a high Cronbach's alpha value (0.786) indicating good reliability. CONCLUSIONS: LENT-SOMA patient questionnaire results agreed well with those from the EORTC QLQ-H&N35 questionnaire for toxicity items where they could be compared explicitly, particularly for subjective endpoints. Patient-reported late toxicity had a negative impact on quality of life. The LENT-SOMA patient questionnaire is both reliable and sensitive to differences between patients treated with different modalities. A patient-based questionnaire is an important contributor to capturing late radiotherapy effects.
    • Effectiveness of a home care nursing program in the symptom management of patients with colorectal and breast cancer receiving oral chemotherapy: a randomized, controlled trial.

      Molassiotis, Alexander; Brearley, Sarah; Saunders, Mark P; Craven, Olive; Wardley, Andrew M; Farrell, Carole; Swindell, Ric; Todd, Chris; Luker, Karen; University of Manchester, School of Nursing, University Place, Manchester, M13 9PL, United Kingdom. alex.molassiotis@manchester.ac.uk (2009-12-20)
      PURPOSE: To assess the effectiveness of a symptom-focused home care program in patients with cancer who were receiving oral chemotherapy in relation to toxicity levels, anxiety, depression, quality of life, and service utilization. PATIENTS AND METHODS: A randomized, controlled trial was carried out with 164 patients with a diagnosis of colorectal (n = 110) and breast (n = 54) cancers who were receiving oral capecitabine. Patients were randomly assigned to receive either a home care program by a nurse or standard care for 18 weeks (ie, six cycles of chemotherapy). Toxicity assessments were carried out weekly for the duration of the patients' participation in the trial, and validated self-report tools assessed anxiety, depression, and quality of life. RESULTS: Significant improvements were observed in the home care group in relation to the symptoms of oral mucositis, diarrhea, constipation, nausea, pain, fatigue (first four cycles), and insomnia (all P < .05). This improvement was most significant during the initial two cycles. Unplanned service utilization, particularly the number of inpatient days (57 v 167 days; P = .02), also was lower in the home care group. CONCLUSION: A symptom-focused home care program was able to assist patients to manage their treatment adverse effects more effectively than standard care. It is imperative that patients receiving oral chemotherapy are supported with such programs, particularly during initial treatment cycles, to improve their treatment and symptom experiences.
    • The impact of radiotherapy late effects on quality of life in gynaecological cancer patients.

      Barker, Claire L; Routledge, Jacqueline A; Farnell, Damian J J; Swindell, Ric; Davidson, Susan E; Department of Clinical Oncology, the Christie NHS Foundation Trust, Manchester, UK. claire.barker@doctors.org.uk (2009-05-19)
      The aims of this study were to assess changes in quality of life (QoL) scores in relation to radical radiotherapy for gynaecological cancer (before and after treatment up to 3 years), and to identify the effect that late treatment effects have on QoL. This was a prospective study involving 225 gynaecological cancer patients. A QoL instrument (European Organisation for the Research and Treatment of Cancer QLQ-C30) and late treatment effect questionnaire (Late Effects Normal Tissues - Subjective Objective Management Analysis) were completed before and after treatment (immediately after radiotherapy, 6 weeks, 12, 24 and 36 months after treatment). Most patients had acute physical symptoms and impaired functioning immediately after treatment. Levels of fatigue and diarrhoea only returned to those at pre-treatment assessment after 6 weeks. Patients with high treatment toxicity scores had lower global QoL scores. In conclusion, treatment with radiotherapy for gynaecological cancer has a negative effect on QoL, most apparent immediately after treatment. Certain late treatment effects have a negative effect on QoL for at least 2 years after radiotherapy. These treatment effects are centred on symptoms relating to the rectum and bowel, for example, diarrhoea, tenesmus and urgency. Future research will identify specific symptoms resulting from late treatment toxicity that have the greatest effect on QoL; therefore allowing effective management plans to be developed to reduce these symptoms and improve QoL in gynaecological cancer patients.
    • The impact of radiotherapy on swallowing and speech in patients who undergo total laryngectomy.

      De Casso, Carmen; Slevin, Nicholas J; Homer, Jarrod J; University Department of Otolaryngology-Head and Neck Surgery, Manchester Royal Infirmary, Manchester, UK. cdecasso@doctors.org.uk (2008-12)
      OBJECTIVES: Quality of life studies have shown no detrimental effect with radiotherapy (RT) in patients who have a total laryngectomy. We wished to determine the effect of RT (initial or postoperative) specifically on the swallowing and voice function in patients treated by total laryngectomy (TL) for carcinoma of the larynx. DESIGN: Multicenter chart review. SETTING: Multicenter study in the Greater Manchester and Lancashire area. PARTICIPANTS: A total of 121 postlaryngectomy patients all of whom had completed definitive treatment at least 6 months before this study. Twenty-six patients had total laryngectomy as a single modality treatment and 95 had total laryngectomy and radiotherapy. MAIN OUTCOME MEASURES: Swallowing (solid food, soft diet or fluid/PEG) and voice development. RESULTS: Swallowing was better in the group who had no radiotherapy (P = 0.0037). There was no difference in voice function between the two groups. We also demonstrated that females had a worse swallowing outcome (P = 0.0101), as did advanced nodal stage (P = 0.001). CONCLUSIONS: RT adversely affects the swallowing results but not the speech results after TL when given either as initial treatment or postoperatively. This should be kept in mind in the decision-making process in the treatment of patients with carcinoma of the larynx.
    • A phase II study evaluating the use of concurrent mitomycin C and capecitabine in patients with advanced unresectable pseudomyxoma peritonei.

      Farquharson, Adam L; Pranesh, Nagarajan; Witham, Gary; Swindell, Ric; Taylor, Malcolm B; Renehan, Andrew G; Rout, Shantanu; Wilson, Malcolm S; O'Dwyer, Sarah T; Saunders, Mark P; et al. (2008-08-19)
      Pseudomyxoma peritonei (PMP) is a rare neoplastic process characterised by progressive intra-abdominal dissemination of mucinous tumour, and generally considered resistant to systemic chemotherapy. A phase II study in patients with advanced unresectable PMP was undertaken to evaluate the combination of systemic concurrent mitomycin C (7 mg m(-2) i.v. on day 1) and capecitabine (1250 mg m(-2) b.d. on days 1-14) in a 3-weekly cycle (MCap). Response was determined by semiquantitative assessment of disease volume on serial computed tomographic (CT) scans and serum tumour marker (CEA, CA125, CA19-9) changes at 12 weeks. Between 2003 and 2006, 40 patients were recruited through a national centre for the treatment of peritoneal surface tumours. At baseline, 23 patients had progressive disease and 17 had stable disease. Of 39 assessable patients, 15 (38%, 95% confidence intervals (CIs): 25, 54%) benefited from chemotherapy in the form of either reductions in mucinous deposition or stabilisation of progressive pretreatment disease determined on CT scan. Notably, two patients, originally considered unresectable, following MCap and re-staging underwent potentially curative cytoreductive surgery. Grade 3/4 toxicity rates were low (6%, 95% CIs: 4, 9%). Twenty out of 29 assessed patients (69%, 95% CIs: 51, 83%) felt that their Global Health Status improved during chemotherapy. This is the first trial to demonstrate an apparent benefit of systemic chemotherapy in patients with advanced unresectable PMP.
    • Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international Phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups.

      Slotman, Berend J; Mauer, Murielle E; Bottomley, Andrew; Faivre-Finn, Corinne; Kramer, Gijs; Rankin, Elaine M; Snee, Michael; Hatton, Matthew; Postmus, Pieter E; Collette, Laurence; et al. (2009-01-01)
      PURPOSE: Prophylactic cranial irradiation (PCI) in patients with extensive-disease small-cell lung cancer (ED-SCLC) leads to significantly fewer symptomatic brain metastases and improved survival. Detailed effects of PCI on health-related quality of life (HRQOL) are reported here. PATIENTS AND METHODS: Patients (age, 18 to 75 years; WHO < or = 2) with ED-SCLC, and any response to chemotherapy, were randomly assigned to either observation or PCI. Health-related quality of life (HRQOL) and patient-reported symptoms were secondary end points. The European Organisation for the Research and Treatment of Cancer core HRQOL tool (Quality of Life Questionnaire C30) and brain module (Quality of Life Questionnaire Brain Cancer Module) were used to collect self-reported patient data. Six HRQOL scales were selected as primary HRQOL end points: global health status; hair loss; fatigue; and role, cognitive and emotional functioning. Assessments were performed at random assignment, 6 weeks, 3 months, and then 3-monthly up to 1 year and 6-monthly thereafter. RESULTS: Compliance with the HRQOL assessment was 93.7% at baseline and dropped to 60% at 6 weeks. Short-term results up to 3 months showed that there was a negative impact of PCI on selected HRQOL scales. The largest mean difference between the two arms was observed for fatigue and hair loss. The impact of PCI on global health status as well as on functioning scores was more limited. For global health status, the observed mean difference was eight points on a scale 0 to 100 at 6 weeks (P = .018) and 3 months (P = .055). CONCLUSION: PCI should be offered to all responding ED SCLC patients. Patients should be informed of the potential adverse effects from PCI. Clinicians should be alert to these; monitor their patients; and offer appropriate support, clinical, and psychosocial care.
    • Randomised phase II trial of 4 dose levels of single agent docetaxel in performance status (PS) 2 patients with advanced non-small cell lung cancer (NSCLC): DOC PS2 trial. Manchester lung cancer group.

      Califano, Raffaele; Griffiths, Richard W; Lorigan, Paul C; Ashcroft, Linda; Taylor, Paul; Burt, Paul A; Lee, Lip W; Chittalia, Abbas; Harris, Maggie A; Faivre-Finn, Corinne; et al. (2011-09)
      The role of chemotherapy for advanced NSCLC patients and ECOG PS2 remains controversial. We evaluated 4 doses of 3-weekly docetaxel to identify a less toxic, clinically effective dose.
    • SCOTCERV: a phase II trial of docetaxel and gemcitabine as second line chemotherapy in cervical cancer.

      Symonds, R P; Davidson, Susan E; Chan, S; Reed, N S; McMahon, T; Rai, D; Harden, S; Paul, J; University of Leicester, Department of Cancer Studies & Molecular Medicine, Leicester, UK. (2011-10)
      The aim of the study was to determine the response rate and response duration of cervical cancer previously treated by cisplatin (with or without radiation) to a combination of docetaxel and gemcitabine. Secondary endpoints were assessment of toxicity and quality of life (QoL) of patients receiving the treatment.
    • Symptom experience in patients with primary brain tumours: a longitudinal exploratory study.

      Molassiotis, Alexander; Wilson, Barbara; Brunton, Lisa; Chaudhary, Haseeb; Gattamaneni, Rao; McBain, Catherine A; University of Manchester, School of Nursing, University Place, Manchester M13 9PL, UK. alex.molassiotis@manchester.ac.uk (2010-12)
      This study was undertaken to further understand the symptom experience and the impact of symptoms in daily life in people treated for brain tumours.
    • Treatment for advanced cervical cancer: Impact on quality of life.

      Davidson, Susan E; The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK. (2010-08-30)
      Cisplatin-based combinations can potentially improve response rates in patients with cervical cancer, but unacceptable toxicity must be avoided. Quality of life (QoL) measures are increasingly used to assess the benefits versus limitations of chemotherapy regimens. A MEDLINE search of English language publications from January 2000 to December 2008 was conducted using the search terms: 'quality of life' OR 'QoL' OR 'HRQoL' AND 'cervical cancer'. Abstracts from the Association of Clinical Oncology meeting, 2008, were also searched. Article inclusion was based on abstract content. Several cervical cancer therapies have shown response rate improvements in combination with cisplatin, including topotecan and paclitaxel. However, only topotecan/cisplatin demonstrates a significant overall survival advantage over cisplatin monotherapy, while both topotecan/cisplatin and paclitaxel/cisplatin demonstrate comparable impact on QoL to cisplatin alone. Few trials of combination chemotherapy for cervical cancer have directly assessed QoL. The combination of topotecan/cisplatin significantly increases overall survival rates without reducing patient QoL.