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BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.
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Background: In 2013, eribulin was reimbursed under a coverage with evidence development (CED) as third or later chemotherapy line for advanced breast cancer (ABC) patients in the Netherlands because of uncertain cost effectiveness. In 2016, the final decision of reimbursing eribulin was taken without considering the evidence collected during CED research. We analysed the cost effectiveness of eribulin versus non-eribulin chemotherapy, using real-world data.Methods: A three health states (progression-free, progressed disease, dead) partitioned survival model was developed. The SOuth East Netherlands Advanced BREast Cancer (SONABRE) registry informed the effectiveness and costs inputs. Health state utility values were obtained from the literature. Incremental cost-effectiveness ratio (ICER) between the eribulin and matched non-eribulin chemotherapy was estimated. Deterministic and probabilistic sensitivity analyses and scenario analyses were performed. The financial risk (i.e., the expected value of perfect information (EVPI) plus the expected monetary loss (eML) associated with reimbursing eribulin) and budget impact associated with reimbursing eribulin were calculated.Results: Eribulin led to higher health benefits (0.07 quality-adjusted life year (QALY)) and costs (15,321) compared with non-eribulin chemotherapy. This resulted in an ICER of 220,608. At a 80,000 per QALY threshold, the risk of reimbursing eribulin was 9,791 per patient (EVPI 13, eML 9,778). Scaled up to the Dutch population, the estimated annual budget impact was 1.9 million and the annual risk of reimbursing eribulin was 2.7 million.Conclusion: From a Dutch societal perspective, eribulin is not cost effective when considering its list price as third and later chemotherapy line for ABC patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Custos de Medicamentos/estatística & dados numéricos , Furanos/uso terapêutico , Cetonas/uso terapêutico , Modelos Econômicos , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/economia , Neoplasias da Mama/mortalidade , Simulação por Computador , Análise Custo-Benefício , Progressão da Doença , Feminino , Furanos/economia , Humanos , Reembolso de Seguro de Saúde/economia , Reembolso de Seguro de Saúde/estatística & dados numéricos , Cetonas/economia , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Intervalo Livre de Progressão , Anos de Vida Ajustados por Qualidade de Vida , Sistema de Registros/estatística & dados numéricosRESUMO
BACKGROUND: The objective of this study was to present initial systemic treatment choices and the outcome of hormone receptor-positive (HR+) metastatic breast cancer. PATIENTS AND METHODS: All the 815 consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight participating hospitals were identified. From the 611 patients with HR+ disease, a total of 520 patients with HER2-negative (HER2-) breast cancer were included. Initial palliative systemic treatment was registered. Progression-free survival (PFS) and overall survival (OS) per initial palliative systemic therapy were obtained using the Kaplan-Meier method and compared using the log-rank test. RESULTS: From the total of 520 patients with HR+/HER2- metastatic breast cancer, 482 patients (93%) received any palliative systemic therapy. Patients that received initial chemotherapy (n = 116) were significantly younger, had less comorbidity, had received more prior adjuvant systemic therapy and were less likely to have bone metastasis only compared with patients that received initial endocrine therapy (n = 366). Median PFS of initial palliative chemotherapy was 5.3 months [95% confidence interval (CI) 4.2-6.2] and of initial endocrine therapy 13.3 months (95% CI 11.3-15.5), with a median OS of 16.1 and 36.9 months, respectively. Initial chemotherapy was also associated with worse outcome in terms of PFS and OS after adjustment for prognostic factors. CONCLUSIONS: A high percentage of patients with HR+ disease received initial palliative chemotherapy, which was associated with worse outcome, even after adjustment of relevant prognostic factors.
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Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cuidados Paliativos/métodos , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Resultado do TratamentoRESUMO
BACKGROUND: We aimed to determine the prognostic impact of time between primary breast cancer and diagnosis of distant metastasis (metastatic-free interval, MFI) on the survival of metastatic breast cancer patients. METHODS: Consecutive patients diagnosed with metastatic breast cancer in 2007-2009 in eight hospitals in the Southeast of the Netherlands were included and categorised based on MFI. Survival curves were estimated using the Kaplan-Meier method. Cox proportional hazards model was used to determine the prognostic impact of de novo metastatic breast cancer vs recurrent metastatic breast cancer (MFI ⩽24 months and >24 months), adjusted for age, hormone receptor and HER2 status, initial site of metastasis and use of prior (neo)adjuvant systemic therapy. RESULTS: Eight hundred and fifteen patients were included and divided in three subgroups based on MFI; 154 patients with de novo metastatic breast cancer, 176 patients with MFI <24 months and 485 patients with MFI >24 months. Patients with de novo metastatic breast cancer had a prolonged survival compared with patients with recurrent metastatic breast cancer with MFI <24 months (median 29.4 vs 9.1 months, P<0.0001), but no difference in survival compared with patients with recurrent metastatic breast cancer with MFI >24 months (median, 29.4 vs 27.9 months, P=0.73). Adjusting for other prognostic factors, patients with MFI <24 months had increased mortality risk (hazard ratio 1.97, 95% CI 1.49-2.60, P<0.0001) compared with patients with de novo metastatic breast cancer. When comparing recurrent metastatic breast cancer with MFI >24 months with de novo metastatic breast cancer no significant difference in mortality risk was found. The association between MFI and survival was seen irrespective of use of (neo)adjuvant systemic therapy. CONCLUSION: Patients with de novo metastatic breast cancer had a significantly better outcome when compared with patients with MFI <24 months, irrespective of the use of prior adjuvant systemic therapy in the latter group. However, compared with patients with MFI >24 months, patients with de novo metastatic breast cancer had similar outcome.
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Neoplasias da Mama/mortalidade , Recidiva Local de Neoplasia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Taxa de SobrevidaRESUMO
Surgical liver resection is a treatment option in patients with resectable colorectal liver metastases. We present two cases of focal nodular hyperplasia (FNH) development after treatment with oxaliplatin during follow-up of colon carcinoma. The first case was a 40-year-old male patient who developed multiple liver lesions suspect for metastatic disease four years after he had undergone laparoscopic right-sided hemicolectomy and adjuvant chemotherapy (capecitabine and oxaliplatin). He underwent a metastasectomy of segments three and four and microwave ablation (MWA) of the lesion in segment one. Pathological analysis demonstrated FNH. The second patient was a 21-year-old woman who presented with multiple liver lesions during follow-up for colon carcinoma. She underwent a laparoscopic right-sided hemicolectomy and was adjuvantly treated with capecitabine and oxaliplatin three years ago. Magnetic resonance imaging (MRI) was performed, and the lesions showed no signs of metastatic disease but were classified as FNH. Therefore, the decision was made to follow up the patient. In conclusion, the development of benign liver lesions could occur during follow-up of colon carcinoma and might be caused by oxaliplatin-induced changes to the liver parenchyma. Hence, it is important to distinguish these from metastatic liver disease.
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A feasibility study was performed to assess the toxicity and efficacy of a combination of gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer (LAPC). 24 patients (15 females and 9 males) with measurable LAPC were included; the median age of the patients was 63 years (range 39-74 years). The performance status ranged from 0 to 2. Gemcitabine was administered at a dose of 300 mg/m(2), concurrent with radiotherapy, three fractions of 8 Gy, on days 1, 8 and 15. When compliance allowed, gemcitabine alone was continued thereafter, at 1000 mg/m(2), weekly times 3, every 4 weeks, depending on the response and toxicity. All patients were evaluable for toxicity and response. The objective response rate was 29.2% (1 complete remission+6 partial remissions); 12 patients had stable disease. However, 2 of the radiological partial remissions were shown to be complete remissions by pathology assessment. Median duration of response was 3 months (range 1-35+months). Median time to progression was 7 months (range 2-37+months). Median survival was 10 months (range 3-37+months). Dose reduction or omission of gemcitabine was necessary in 10 patients. Non-haematological toxicity consisted of 87.5% nausea and vomiting grade I-II, diarrhoea 54%, ulceration in stomach and duodenum 37.5% (20.8% ulceration with bleeding); 1 patient developed a fistula between the duodenum and aorta, 5 months after treatment. Anaemia grade III-IV was observed in 8.3% of the patients. Neutropenia grade III-IV was observed in 8.3%, thrombocytopenia grades III-IV in 16.7%. In 1 patient who underwent resection postchemoradiation, no viable tumour cells were found. In addition, in the patient who suddenly died of a fistula between the duodenum and aorta, no viable tumour cells were detectable at autopsy. Although the toxicity of this treatment was occasionally severe, the response and survival are encouraging and warrant further studies of this combination.
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Antimetabólitos Antineoplásicos/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/radioterapia , Radiossensibilizantes/administração & dosagem , Adulto , Idoso , Antimetabólitos Antineoplásicos/efeitos adversos , Terapia Combinada/métodos , Desoxicitidina/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiossensibilizantes/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
A patient with a large duodenal melanoma metastasis, involving adjacent jejunum and colon, is presented. Treatment consisted of a combination of radical surgery and active specific immunotherapy by means of an autologous tumor cell vaccine and BCG after which a recurrence-free survival of now more than 10 years has been observed. The role of surgery and immunotherapy in the treatment of metastatic melanoma are discussed.
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Vacinas Anticâncer/uso terapêutico , Neoplasias Duodenais/terapia , Imunoterapia Ativa , Melanoma/terapia , Adenocarcinoma/cirurgia , Adulto , Vacina BCG/uso terapêutico , Neoplasias da Mama/cirurgia , Neoplasias Duodenais/diagnóstico , Neoplasias Duodenais/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Melanoma/diagnóstico , Melanoma/cirurgia , Segunda Neoplasia Primária/cirurgiaRESUMO
BACKGROUND: Irinotecan is an active drug in colorectal cancer. In patients with liver metastases, hepatic arterial infusion of irinotecan could theoretically result in higher exposure to the drug. In order to determine the efficacy of hepatic arterial irinotecan we conducted a phase II study in pretreated patients with liver metastases of colorectal cancer. PATIENTS AND METHODS: Patients with measurable liver metastases of colorectal cancer with World Health Organization performance status (WHO PS) <2 were treated with a 5-day continuous infusion of hepatic arterial irinotecan every 3 weeks at a dose of 20 mg/m(2)/day. RESULTS: Of the 25 patients included, 22 were evaluable for response. Three of 22 patients (13.6%) had a partial response, nine (40.9%) had stable disease and 10 (45.4%) had progressive disease. No complete responses were observed. Median time to progression was 2.8 (range 1.2-23.8) months. Major toxicities were vomiting and diarrhea. There was no major hematological toxicity. CONCLUSIONS: Five-day continuous hepatic arterial infusion of irinotecan 20 mg/m(2)/day has low activity in patients with liver metastases of colorectal cancer previously treated by chemotherapy.