Comanagement Strategy Between Academic Institutions and Community Practices to Reduce Induction Mortality in Acute Promyelocytic Leukemia.

PURPOSE: Acute promyelocytic leukemia (APL) is a curable leukemia with > 90% survival in clinical trials. Population-based studies from Sweden and US SEER data have shown long-term survival rates of 62% and 65.7%, with the lower rate being from a higher percentage of early deaths. METHODS: In this prospective, multicenter trial, we developed a simplified algorithm that focused on prevention and early treatment of the three main causes of death: bleeding, differentiation syndrome, and infection. All patients with a diagnosis of APL were included. The initial 6 months were spent educating oncologists about early deaths in APL. At the time of suspicion of an APL, an expert was contacted. The algorithm was made available followed by discussion of the treatment plan. Communication between expert and treating physician was frequent in the first 2 weeks, during which time most deaths take place. RESULTS: Between September 2013 and April 2016, 120 patients enrolled in the study from 32 hospitals. The median age was 52.5 years, with 39% > 60 years and 25% with an age-adjusted Charlson comorbidity index > 4. Sixty-three percent of patients were managed at community centers. Two patients did not meet the criteria for analysis, and of 118 evaluable patients, 10 died, with an early mortality rate of 8.5%. With a median follow-up of 27.3 months, the overall survival was 84.5%. CONCLUSION: Induction mortality can be decreased and population-wide survival improved in APL with the use of standardized treatment guidelines. Support from experts who have more experience with induction therapy is crucial and helps to improve the outcomes.

Randomized study of concurrent carboplatin, paclitaxel, and radiotherapy with or without prior induction chemotherapy in patients with locally advanced non-small cell lung cancer.

BACKGROUND: Multiple concepts of combined modality therapy for locally advanced inoperable non-small cell lung cancer have been investigated. These include induction chemotherapy, concomitant chemo-radiotherapy, and radiation only. To date, combined modality therapy specially the use of concomitant chemo-radiotherapy has led to promising results and was shown to be superior to radiotherapy alone in phase II studies. However the optimum chemo-therapeutic regimen to be used as well as the benefit of induction chemotherapy before concomitant chemo-radiotherapy are yet to be determined. Based on these observations, we investigated the use of paclitaxel and carboplatin concomitantly with radiotherapy and the benefit of prior two cycles induction chemotherapy. MATERIALS AND METHODS: In this trial 60 patients with locally advanced inoperable non small cell lung cancer, good performance status and minimal weight loss have been randomized into 3 groups each of 20 patients. Group A received induction 2 cycles paclitaxel (175 mg/m2) and carboplatin (AUC 6) on day 1 and 28th followed by concomitant paclitaxel (45 mg/m2) and carboplatin (AUC 2) weekly with radiotherapy. Group B received concomitant carboplatin, paclitaxel (same doses as in group A) and radiotherapy with no prior induction chemotherapy. Group C received only radiotherapy to a total dose of 60 Gy in conventional fractionation. RESULTS: A total of 60 patients were enrolled in this study between 1998 and 2000. Pretreatment characteristics, including age, gender, performance status, histological features and stage were comparable in each group. The incidence of oesophagitis was significantly higher in group A and B than in group C (p=0.023). Hematological toxicities was also significantly higher in group A & B than in group C (p=0.003). The response rate was significantly higher in group A and B than in group C (75%, 79%, and 40% respectively) (p=0.020). The time to in-field progression was significantly higher in group B as compared to group A (48% vs. 32% failure in 2 years respectively) (p=0.000). The median 2 year survival was significantly higher in group A and B than in group C (p=0.039) but no statistical difference was seen between group A and B. CONCLUSION: Combined chemo-radiotherapy resulted in better response and survival as compared to conventional radiotherapy in the treatment of locally advanced nonsmall cell lung cancer. Early initiation of radiation with concomitant chemotherapy resulted in prolonged time to infield progression. On the other hand, two cycles of induction chemotherapy did not show any significant difference regarding the response or survival. Weekly paclitaxel and carboplatin plus radiotherapy is a well tolerated regimen for outpatients with encouraging results.