RESUMO
BACKGROUND: Peptide receptor radionuclide therapy (PRRT) has shown favorable results in neuroendocrine tumors (NETs). Long-term safety and efficacy data for 177 Lu-octreotate PRRT, particularly in combination with chemotherapy, is lacking. METHODS: The authors conducted a retrospective review of the long-term toxicity and survival outcomes of 104 patients with advanced NETs treated on 4 phase 2 clinical trials with Lutetium-177-octreotate (177 Lu-octreotate) PRRT, mostly in combination with chemotherapy. Median follow-up was 68 months, which represents the longest follow-up study of 177 Lu-octreotate PRRT for NETs to date. RESULTS: Median progression-free survival (PFS) was 37 months, and median overall survival (OS) was 71 months. Five- and 10-year OS were 62% and 29%, and 5- and 10-year PFS were 36% and 21%, respectively, demonstrating 177 Lu-octreotate can provide durable responses. PRRT was well tolerated with 1.9% of patients developing chronic renal impairment and 1% of patients developing long-term thrombocytopenia. Interestingly, there was a relatively high rate of myelodysplasia (MDS)/leukemia (6.7%), possibly attributable to the longer follow-up (with all except 1 case occurring more than 4 years after PRRT treatment) or to the addition of concurrent chemotherapy. CONCLUSIONS: Lutetium-177-Octreotate PRRT remains an efficacious and well tolerated treatment in long-term follow-up. For clinicians deciding on the timing of PRRT for individual patients, the 6.7% long-term risk of MDS/leukemia needs to be balanced against the 21% PFS at 10 years.
Assuntos
Leucemia , Tumores Neuroendócrinos , Compostos Organometálicos , Seguimentos , Humanos , Leucemia/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/radioterapia , Octreotida/efeitos adversos , Compostos Organometálicos/efeitos adversos , Radioisótopos/efeitos adversosAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Hipercalcemia/tratamento farmacológico , Neoplasias das Paratireoides/complicações , Ligante RANK/antagonistas & inibidores , Denosumab , Evolução Fatal , Humanos , Hipercalcemia/etiologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/diagnóstico , Neoplasias das Paratireoides/patologia , Neoplasias Pleurais/complicações , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/secundário , Neoplasias da Glândula Tireoide/secundárioRESUMO
BACKGROUND: Second-line treatment with irinotecan for advanced or metastatic colorectal cancer prolongs survival. It is uncertain whether irinotecan is better administered with 5-fluorouracil or alone in patients previously treated with a fluoropyrimidine. We compared toxicity (particularly diarrhoea), quality of life, and efficacy of combination chemotherapy and irinotecan in these patients. METHODS: In DaVINCI, a randomised phase II trial, patients with advanced colorectal cancer were randomly allocated to: Combination therapy (FOLFIRI), irinotecan (180 mg/m(2) IV over 90 min, day 1), 5-fluorouracil (400mg/m(2) IV bolus and 2400 mg/m(2) by 46-hour infusion from day 1) and folinic acid (20mg/m(2) IV bolus, day 1), 2-weekly; or Single-agent, irinotecan (350 mg/m(2) IV over 90 min), 3-weekly. Toxicity was evaluated every treatment cycle; QOL and response 6-weekly. Analysis was by intention to treat. The trial, amended from a larger factorial design, was terminated early due to slow recruitment. Results were also combined with other second-line irinotecan trials. FINDINGS: We randomised 44 patients to combination and 45 to single agent. Eight patients in the irinotecan arm and 4 in the combination arm had grade 3/4 diarrhoea (P=0.24). Treatment groups did not differ significantly in overall QOL changes, response rate or progression free or overall-survival. In a systematic review of 29 trials of second-line irinotecan-based treatment, single-agent irinotecan was associated with more diarrhoea and alopecia than the combination but efficacy was similar. INTERPRETATION: Combination treatment compared with single-agent irinotecan reduces alopecia and diarrhoea without compromising efficacy on clinical outcomes. Both regimens remain as reasonable treatment options. FUNDING: Research grant (Pfizer).