The lancet oncology

Publications in this journal

• Article: Effects of a programme of interventions on regional comprehensive palliative care for patients with cancer: a mixed-methods study.

  Tatsuya Morita, Mitsunori Miyashita, Akemi Yamagishi, Miki Akiyama, Nobuya Akizuki, Kei Hirai, Chizuru Imura, Masashi Kato, Yoshiyuki Kizawa, Yutaka Shirahige, Takuhiro Yamaguchi, Kenji Eguchi
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  ABSTRACT: BACKGROUND: Improvement of palliative care is an important public health issue, but knowledge about how to deliver palliative care throughout a region remains inadequate. We used surveys and in-depth interviews to assess changes in the quality of palliative care after regional interventions and to gain insights for improvement of palliative care at a regional level. METHODS: In this mixed-methods study, a comprehensive programme of interventions for regional palliative care for patients with cancer was implemented from April 1, 2008, to March 31, 2011 in Tsuruoka, Kashiwa, Hamamatsu, and Nagasaki in Japan. Interventions included education, specialist support, and networking. We surveyed patients, bereaved family members, physicians, and nurses before and after the interventions were introduced. We also did qualitative interviews with health-care professionals after the interventions were introduced. Primary endpoints were numbers of home deaths, coverage of specialist services, and patient-reported and family-reported qualities of care. This trial is registered with UMIN Clinical Trial Registry, Japan (UMIN000001274). FINDINGS: 859 patients, 1110 bereaved family members, 911 physicians, and 2378 nurses provided analysable preintervention surveys; 857 patients, 1137 bereaved family members, 706 physicians, and 2236 nurses provided analysable postintervention surveys. Proportions of home deaths increased significantly, from 348 of 5147 (6·76%) before the intervention programme to 581 of 5546 (10·48%) after the intervention programme (p<0·0001). Furthermore, 194 of 221 (87·78%) family members of patients who died at home answered that these patients had wanted to die at home. The ratio of patients who received palliative care services to all patients who died of cancer increased significantly (from 0·31 to 0·50; p<0·0001). The patient-reported (effect size 0·14; adjusted p 0·0027) and family-reported (0·23; <0·0001) qualities of care were significantly better after interventions than before interventions. Physician-reported and nurse-reported difficulties decreased significantly after the introduction of the interventions. Qualitative interviews showed improved communication and cooperation between health-care professionals because of greater opportunities for interactions at various levels. INTERPRETATION: A regional programme of interventions could improve the quality of palliative care. Improvement of communication between health-care professionals is key to improvement of services. FUNDING: Third Term Comprehensive Control Research for Cancer Health and Labor Sciences Research Grants of the Ministry of Health, Labour and Welfare of Japan.
  The lancet oncology 05/2013;
• Article: Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial.

  Jie Jin, Jian-Xiang Wang, Fei-Fei Chen, De-Pei Wu, Jiong Hu, Jian-Feng Zhou, Jian-Da Hu, Jian-Min Wang, Jian-Yong Li, Xiao-Jun Huang, [......], Yin-Jun Lou, Wan-Mao Ni, Hong-Yan Tong, Hua-Feng Wang, Ying-Chang Mi, Xin Du, Bao-An Chen, Yi Shen, Zhu Chen, Sai-Juan Chen
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  ABSTRACT: BACKGROUND: Homoharringtonine-based induction regimens have been widely used in China for patients with acute myeloid leukaemia. However, their efficacy has not been tested in a multicentre randomised controlled trial in a large population. We assessed the efficacy and safety of homoharringtonine-based induction treatment for management of newly diagnosed acute myeloid leukaemia. METHODS: This open-label, randomised, controlled, phase 3 study was done in 17 institutions in China between September, 2007, and July, 2011. Untreated patients aged 14-59 years with acute myeloid leukaemia were randomly assigned (by a computer-generated allocation schedule without stratification) to receive one of three induction regimens in a 1:1:1 ratio: homoharringtonine 2 mg/m(2) per day on days 1-7, cytarabine 100 mg/m(2) per day on days 1-7, and aclarubicin 20 mg/day on days 1-7 (HAA); homoharringtonine 2 mg/m(2) per day on days 1-7, cytarabine 100 mg/m(2) per day on days 1-7, and daunorubicin 40 mg/m(2) per day on days 1-3 (HAD); or daunorubicin 40-45 mg/m(2) per day on days 1-3 and cytarabine 100 mg/m(2) per day on days 1-7 (DA). Patients in complete remission were offered two cycles of intermediate-dose cytarabine (2 g/m(2) every 12 h on days 1-3). The primary endpoints were the proportion of patients who achieved complete remission after two cycles of induction treatment and event-free survival in the intention-to-treat population. The trial is registered in the Chinese Clinical Trial Register, number ChiCTR-TRC-06000054. FINDINGS: We enrolled 620 patients, of whom 609 were included in the intention-to-treat analysis. 150 of 206 patients (73%) in the HAA group achieved complete remission versus 125 of 205 (61%) in the DA group (p=0·0108); 3-year event-free survival was 35·4% (95% CI 28·6-42·2) versus 23·1% (95% CI 17·4-29·3; p=0·0023). 133 of 198 patients (67%) in the HAD group had complete remission (vs DA, p=0·20) and 3-year event-free survival was 32·7% (95% CI 26·1-39·5; vs DA, p=0·08). Adverse events were much the same in all groups, except that more patients in the HAA (12 of 206 [5·8%]) and HAD (13 of 198 [6·6%]) groups died within 30 days than in the DA group (two of 205 [1%]; p=0·0067 vs HAA; p=0·0030 vs HAD). INTERPRETATION: A regimen of homoharringtonine, cytarabine, and aclarubicin is a treatment option for young, newly diagnosed patients with acute myeloid leukaemia. FUNDING: Chinese National High Tech Programme, Key Special Research Foundation of the Ministry of Science and Technology of China, National Nature Science Foundation of China, National Clinical Key Specialty Construction Project.
  The lancet oncology 05/2013;
• Article: Is there a standard induction regimen for patients with AML?

  Farhad Ravandi, Jorge Cortes, Hagop Kantarjian
  The lancet oncology 05/2013;
• Article: Cytokine patterns in patients with cancer: a systematic review.

  Bodo E Lippitz
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  ABSTRACT: Active, but dysfunctional, immune responses in patients with cancer have been studied in several tumour types, but owing to the heterogeneity of cancer theories of common reaction mechanisms seem to be obsolete. In this Review of published clinical studies of patients with cancer, expression and interplay of the following cytokines are examined: interleukin 2, interleukin 6, interleukin 8, interleukin 10, interleukin 12, interleukin 18, tumour necrosis factor α (TNFα), transforming growth factor β (TGFβ), interferon-γ, HLA-DR, macrophage migration inhibitory factor (MIF), and C-X-C motif chemokine receptor 4 (CXCR4). Clinical data were analysed in a non-quantitative descriptive manner and interpreted with regard to experimentally established physiological cytokine interactions. The clinical cytokine pattern that emerged suggests that simultaneous immunostimulation and immunosuppression occur in patients with cancer, with increased concentrations of the cytokines MIF, TNFα, interleukin 6, interleukin 8, interleukin 10, interleukin 18, and TGFβ. This specific cytokine pattern seems to have a prognostic effect, since high interleukin 6 or interleukin 10 serum concentrations are associated with negative prognoses in independent cancer types. Although immunostimulatory cytokines are involved in local cancer-associated inflammation, cancer cells seem to be protected from immunological eradication by cytokine-mediated local immunosuppression and a resulting defect of the interleukin 12-interferon-γ-HLA-DR axis. Cytokines produced by tumours might have a pivotal role in this defect. A working hypothesis is that the cancer-specific and histology-independent uniform cytokine cascade is one of the manifestations of the underlying paraneoplastic systemic disease, and this hypothesis links the stage of cancer with both the functional status of the immune system and the patient's prognosis. Neutralisation of this cytokine pattern could offer novel and so far unexploited treatment approaches for cancer.
  The lancet oncology 05/2013; 14(6):e218-28.
• Article: Is India ready to lead the battle for fair access to medicines?

  The Lancet Oncology
  The lancet oncology 05/2013; 14(6):437.
• Article: Relapsed childhood acute lymphoblastic leukaemia.

  Deepa Bhojwani, Ching-Hon Pui
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  ABSTRACT: With steadily improved cure rates for children with newly diagnosed acute lymphoblastic leukaemia (ALL), treating relapsed ALL has become increasingly challenging largely due to resistance to salvage therapy. Improved biological understanding of mechanisms of relapse and drug resistance, the identification of actionable molecular targets by studying leukaemic cell and host genetics, precise risk stratification with minimum residual disease measurement, and the development of new therapeutic drugs and approaches are needed to improve outcomes of relapsed patients. Molecularly targeted therapies and innovative immunotherapeutic approaches that include specialised monoclonal antibodies and cellular therapies hold promise of enhanced leukaemia cell killing with non-overlapping toxicities. Advances in preparative regimens, donor selection, and supportive care should improve the success of haemopoietic stem-cell transplantation for high-risk patients.
  The lancet oncology 05/2013; 14(6):e205-17.
• Article: Chocolate: delicious beauty or harmful beast?

  Justin Stebbing, Venkatesh Gajapathy, Charles Lowdell
  The lancet oncology 05/2013; 14(6):457-8.
• Article: Non-invasive ventilation for end-of-life oncology patients.

  Arun Azad, Michael Franco
  The lancet oncology 05/2013; 14(6):e199-200.
• Article: Radiotherapy capacity in Europe.

  Cai Grau, Josep M Borras, Julian Malicki, Ben Slotman, Peter Dunscombe, Mary Coffey, Donal Hollywood, Ferran Guedea, Chiara Gasparotto, Yolande Lievens
  The lancet oncology 05/2013; 14(6):e196-8.
• Article: Protein phosphatase 2A: a target for anticancer therapy.

  Danilo Perrotti, Paolo Neviani
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  ABSTRACT: Protein phosphatase 2A (PP2A), one of the main serine-threonine phosphatases in mammalian cells, maintains cell homoeostasis by counteracting most of the kinase-driven intracellular signalling pathways. Unrestrained activation of oncogenic kinases together with inhibition of tumour suppressors is often required for development of cancer. PP2A has been shown to be genetically altered or functionally inactivated in many solid cancers and leukaemias, and is therefore a tumour suppressor. For example, the phosphatase activity of PP2A is suppressed in chronic myeloid leukaemia and other malignancies characterised by aberrant activity of oncogenic kinases. Preclinical studies show that pharmacological restoration of PP2A tumour-suppressor activity by PP2A-activating drugs (eg, FTY720) effectively antagonises cancer development and progression. Here, we discuss PP2A as a druggable tumour suppressor in view of the possible introduction of PP2A-activating drugs into anticancer therapeutic protocols.
  The lancet oncology 05/2013; 14(6):e229-38.
• Article: Has the time come for metronomics in low-income and middle-income countries?

  Nicolas André, Shripad Banavali, Yuliya Snihur, Eddy Pasquier
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  ABSTRACT: In 2008, 72% of cancer deaths occurred in low-income and middle-income countries, where, although there is a lower incidence of cancer than in high-income countries, survival rates are also low. Many patients are sent home to die, and an even larger number of patients do not have access to treatment facilities. New constraint-adapted therapeutic strategies are therefore urgently needed. Metronomic chemotherapy-the chronic administration of chemotherapy at low, minimally toxic doses on a frequent schedule of administration, with no prolonged drug-free breaks-has recently emerged as a potential strategy to control advanced or refractory cancer and represents an alternative for patients with cancer living in developing countries. This low-cost, well-tolerated, and easy to access strategy is an attractive therapeutic option in resource-limited countries. Moreover, combined with drug repositioning, additional anticancer effects can be achieved, ultimately resulting in improved cancer control while maintaining minimum cost of treatment. In this Personal View, we will briefly review the rationale behind the combination of metronomic chemotherapy and drug repositioning-an approach we term metronomics. We assess the clinical experience obtained with this kind of anticancer treatment and describe potential new developments in countries with limited resources. We also highlight the need for adapted clinical study endpoints and innovative models of collaboration between for-profit and non-profit organisations, to address the growing problem of cancer in resource-limited countries.
  The lancet oncology 05/2013; 14(6):e239-48.
• Article: Pancreaticoduodenectomy: time to change our approach?

  Christopher L Wolfgang, Timothy M Pawlik
  The lancet oncology 05/2013;
• Article: Radiotherapy capacity in Europe - Authors' reply.

  Eduardo Rosenblatt, Joanna Izewska, Yavuz Anacak, Yaroslav Pynda, Pierre Scalliet, Mathieu Boniol, Philippe Autier
  The lancet oncology 05/2013; 14(6):e198-9.
• Article: Radiotherapy capacity in Europe.

  Haris Charalambous, Yiola Marcou, Nicos Katodritis, Panteleimon Kountourakis, Demetris Andreopoulos
  The lancet oncology 05/2013; 14(6):e196.
• Article: A selective ALK inhibitor in ALK-rearranged patients.

  James Chih-Hsin Yang
  The lancet oncology 04/2013;
• Article: CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-001JP study): a single-arm, open-label, phase 1-2 study.

  Takashi Seto, Katsuyuki Kiura, Makoto Nishio, Kazuhiko Nakagawa, Makoto Maemondo, Akira Inoue, Toyoaki Hida, Nobuyuki Yamamoto, Hiroshige Yoshioka, Masao Harada, Yuichiro Ohe, Naoyuki Nogami, Kengo Takeuchi, Tadashi Shimada, Tomohiro Tanaka, Tomohide Tamura
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  ABSTRACT: BACKGROUND: Currently, crizotinib is the only drug that has been approved for treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). We aimed to study the activity and safety of CH5424802, a potent, selective, and orally available ALK inhibitor. METHODS: In this multicentre, single-arm, open-label, phase 1-2 study of CH5424802, we recruited ALK inhibitor-naive patients with ALK-rearranged advanced NSCLC from 13 hospitals in Japan. In the phase 1 portion of the study, patients received CH5424802 orally twice daily by dose escalation. The primary endpoints of the phase 1 were dose limiting toxicity (DLT), maximum tolerated dose (MTD), and pharmacokinetic parameters. In the phase 2 portion of the study, patients received CH5424802 at the recommended dose identified in the phase 1 portion of the study orally twice a day. The primary endpoint of the phase 2 was the proportion of patients who had an objective response. Treatment was continued in 21-day cycles until disease progression, intolerable adverse events, or withdrawal of consent. The analysis was done by intent to treat. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-101264. FINDINGS: Patients were enrolled between Sept 10, 2010, and April 18, 2012. The data cutoff date was July 31, 2012. In the phase 1 portion, 24 patients were treated at doses of 20-300 mg twice daily. No DLTs or adverse events of grade 4 were noted up to the highest dose; thus 300 mg twice daily was the recommended phase 2 dose. In the phase 2 portion of the study, 46 patients were treated with the recommended dose, of whom 43 achieved an objective response (93·5%, 95% CI 82·1-98·6) including two complete responses (4·3%, 0·5-14·8) and 41 partial responses (89·1%, 76·4-96·4). Treatment-related adverse events of grade 3 were recorded in 12 (26%) of 46 patients, including two patients each experiencing decreased neutrophil count and increased blood creatine phosphokinase. Serious adverse events occurred in five patients (11%). No grade 4 adverse events or deaths were reported. The study is still ongoing, since 40 of the 46 patients in the phase 2 portion remain on treatment. INTERPRETATION: CH5424802 is well tolerated and highly active in patients with advanced ALK-rearranged NSCLC. FUNDING: Chugai Pharmaceutical Co, Ltd.
  The lancet oncology 04/2013;
• Article: Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial.

  Thomas Crosby, Christopher N Hurt, Stephen Falk, Simon Gollins, Somnath Mukherjee, John Staffurth, Ruby Ray, Nadim Bashir, John A Bridgewater, J Ian Geh, David Cunningham, Jane Blazeby, Rajarshi Roy, Tim Maughan, Gareth Griffiths
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  ABSTRACT: BACKGROUND: Definitive chemoradiotherapy (CRT) is an alternative to surgery for the curative treatment of oesophageal carcinoma. The SCOPE1 trial aimed to investigate the addition of cetuximab to cisplatin and fluoropyrimidine-based definitive CRT in patients with localised oesophageal squamous-cell cancer and adenocarcinomas to assess activity, safety, and feasibility of use. METHODS: In this multicentre, randomised, open-label, phase 2/3 trial, we recruited patients aged 18 years and older from UK radiotherapy centres who had non-metastatic, histologically confirmed carcinoma of the oesophagus (adenocarcinoma, squamous-cell, or undifferentiated; WHO status 0-1; stage I-III disease) and been selected to receive definitive CRT. Patients were randomly assigned (1:1) via a central computerised system using stratified minimisation (with an 80:20 random element) to receive CRT alone or CRT with cetuximab (400 mg/m(2) on day 1 followed by 250 mg/m(2) weekly), stratified by recruiting hospital, primary reason for not having surgery, tumour histology, and tumour stage. CRT consisted of cisplatin 60 mg/m(2) (day 1) and capecitabine 625 mg/m(2) twice daily (days 1-21) for four cycles; cycles three and four were given concurrently with 50 Gy in 25 fractions of radiotherapy. The primary endpoint was the proportion of patients who were treatment failure free at week 24 for the phase 2 trial and overall survival for the phase 3 trial, both measured from randomisation. We analysed data by intention to treat. This trial is an International Standard Randomised Controlled Trial, number 47718479. FINDINGS: 258 patients (129 assigned to each treatment group) from 36 UK centres were recruited between Feb 7, 2008, and Feb 22, 2012. Recruitment was stopped without continuation to phase 3 because the trial met criteria for futility, but we continued to follow-up recruited patients until all had reached at least 24-week follow-up (median follow-up of patients who survived was 16·8 months [IQR 11·2-24·5]). Fewer patients were treatment failure free at 24 weeks in the CRT plus cetuximab group (79 of 119 patients [66·4%, 90% CI 58·6-73·6]) than in the CRT only group (93 of 121 patients [76·9%, 69·7-83·0]). The CRT plus cetuximab group also had shorter median overall survival (22·1 months [95% CI 15·1-24·5] vs 25·4 months [20·5-37·9]; adjusted HR 1·53 [95% CI 1·03-2·27]; p=0·035). Patients who received CRT plus cetuximab had more non-haematological grade 3 or 4 toxicities (102 [79%] of 129 patients vs 81 [63%] of 129 patients; p=0·004). The most common grade 3 or 4 toxicities were low white blood cell count (14 [11%] in the CRT plus cetuximab group vs 21 [16%] in the CRT only group), low absolute neutrophil count (15 [12%] vs 24 [19%]), fatigue (26 [20%] vs 25 [19%]), and dysphagia (35 [27%] vs 37 [29%]). INTERPRETATION: The addition of cetuximab to standard chemotherapy and radiotherapy cannot be recommended for patients with oesophageal cancer suitable for definitive CRT. FUNDING: Cancer Research UK.
  The lancet oncology 04/2013;
• Article: Targeted therapy and chemoradiotherapy in oesophageal cancer.

  Bryan H Burmeister, Sandro V Porceddu
  The lancet oncology 04/2013;
• Article: It's time to quit.

  The Editors
  The lancet oncology 04/2013;