Long-term survivors with advanced nonsquamous non-small cell lung cancer (nsNSCLC) treated with first-line (1L) chemotherapy (CT) plus bevacizumab (B) and maintenance (mtc) B.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18055-e18055
Author(s):  
Javier de Castro ◽  
Dolores Isla ◽  
Jose Luis Gonzalez Larriba ◽  
Sergio Vazquez Estevez ◽  
Bartomeu Massuti ◽  
...  

e18055 Background: B plus CT followed by mtc B has been shown to improve outcomes in patients (pts) with nsNSCLC. In the clinical setting, some pts are able to receive prolonged mtc treatment (Tx) with B. The aim of our research was to explore their clinical characteristics, in order to assess the behavior of these pts who benefit most from B. Methods: In 30 Spanish institutions we studied retrospectively data from 104 pts with advanced nsNSCLC receiving long-time mtc B defined by a PFS ≥ 9 months (m), which represents an increase in PFS of approximately 50%, as compared with historical data. Clinical and histological characteristics, Tx received, ORR, median PFS and OS, and safety data were recorded. Results: Pts characteristics: median age 57 years (yr); caucasian: 98%; ECOG PS 0/1/2 (%): 61/38/2; male: 61%; current/former/never smokers (%): 36/45/19; baseline hypertension (HTN)/cardiovascular disease (%): 24/9; adenocarcinoma: 82%; stage IV: 84%; 84% of pts presented ≤2 metastatic sites; central tumor location: 30%; tumor cavitation: 4%; among 40 pts tested, 8% presented activating EGFR mutations. 1L CT was: carboplatin/cisplatin doublets (%): 57/43; median no. of cycles for CT/B and mtc B was 6 and 18, respectively. Median B dose was 7.5 mg/kg. ORR: 83%. Of 71% of pts who had evidence of PD to 1L, 90% received second-line (2L) Tx. 77% of pts who progressed to 2L, received a third-line (3L). B was maintained in 26% and 24% of pts receiving 2L and 3L. Median PFS: 15 m (CI 95%:14-16); median OS: 31 m (95% CI: 22-39). 1 and 2 yrs survival rates (%): 97 (95% CI: 93 - 100) and 62 (95% CI: 51 - 73). Most frequent B related toxicities (%): gr 1/2 epistaxis (22/0), gr 1/2 HTN (12/6), grade 1/2/3 asthenia (2/6/4) and gr 1/2/3 proteinuria (3/3/1). Conclusions: To our knowledge, these are the first data reported of long-term survivors with advanced nsNSCLC treated with 1L CT/B plus long-time mtc B. Although prospective evaluation is required, the outstanding median OS (31 m) and 2-yr survival (62%) point out the importance of selecting Tx and the role of mtc B after 1LB. B was very well tolerated, without significant life-threatening toxicities. Subgroup analyses will be presented.

1988 ◽  
Vol 6 (10) ◽  
pp. 1630-1635 ◽  
Author(s):  
J A Wilimas ◽  
E C Douglass ◽  
S Lewis ◽  
D Fairclough ◽  
G Fullen ◽  
...  

From 1968 to 1986, 192 patients from 0 to 17 years of age were enrolled in three consecutive protocol-controlled studies of Wilms' tumor at St Jude Children's Research Hospital. Tumors were completely excised at the time of diagnosis whenever possible, and patients were subsequently treated with chemotherapy and radiotherapy according to the initial extent of disease. All patients received dactinomycin and vincristine, with doxorubicin added to the regimens in studies 2 and 3. Chemotherapy was extended to 18 months in study 2 (n = 53), but was limited to 12 months for most patients in study 3 (n = 107). In the third study, radiation was eliminated altogether for patients with stage I or II tumors and was reduced to 12 Gy for those with more advanced disease. Intensification of chemotherapy in study 2 improved the 5-year relapse-free survival rate over that in study 1 (82% v 52%), but the accompanying increase in toxicity was considered unacceptable. Comparison of 2-year relapse-free survival rates in studies 2 and 3 indicated that the reduction of therapy in the latter trial did not jeopardize disease control: 88% v 86% for patients with stage II or III disease, favorable histology; 75% v 57% for the same stages, unfavorable histology; and 57% v 61% for stage IV patients. At least 80% of all patients enrolled in study 3 will be long-term survivors. We conclude that rescheduling of effective antitumor drugs and eliminating or reducing radiotherapy are feasible alternatives in the treatment of Wilms' tumor with favorable histologic features.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 113-113
Author(s):  
Takeshi Kawakami ◽  
Shun Yamamoto ◽  
Seiichiro Mitani ◽  
Taito Esaki ◽  
Yasushi Tsuji ◽  
...  

113 Background: BBP has been recognized as one of the standard 2nd-line treatment strategy for pts with mCRC based on the ML18147 trial. However, this trial excluded pts with disease progression < 3 months in the 1st-line BEV-containing chemotherapy. Methods: The subjects were mCRC pts who received the 2nd-line chemotherapy after experiencing disease progression < 100 days in the 1st-line BEV-containing chemotherapy between Apr 2010 and Dec 2016. This multi-institutional retrospective study compared the efficacy and safety between the 2nd-line chemotherapy with BEV (BBP) and without BEV (non-BBP), adjusting ECOG PS, WBC, ALP, number of metastatic sites, RAS status, and sidedness using Cox proportional hazard model. Results: 61 pts were evaluated. Patients' backgrounds were numerically different between BBP (n = 36) and non-BBP (n = 25), such as PS (0-1/2≤/unknown: 89/8/3 and 56/40/4%) and RASstatus (wild/mutant/unknown: 28/56/16 and 76/16/8%). There were no significant differences in age (median: 59 and 57), sex (male/female: 53/47 and 32/68%), tumor location (right/left: 44/56 and 40/60%), disease status (stage IV/recurrence: 67/33 and 84/16%), number of metastatic sites (1/2≤: 33/67 and 20/80%), the 1st-line regimens (oxaliplatin-based/irinotecan-based: 83/17 and 96/4%) between two arms. The 2nd-line chemotherapy regimens with EGFR antibody-containing/cytotoxic alone were 64/36% in non-BBP, respectively. The response rates were 5.9 and 8.7% in BBP and non-BBP. Median PFS were 3.7 and 2.8 months (HR 0.83, 95%CI 0.49-1.41, p = 0.486; adjusted HR 0.97, 95%CI 0.48-1.96, p = 0.932), respectively. The proportions of pts who received subsequent chemotherapy were 58 and 32% (p = 0.068). Median OS were 7.6 and 5.4 months (HR 0.70, 95%CI 0.41-1.19, p = 0.193; adjusted HR 0.65, 95%CI 0.34-1.25, p = 0.195). Common grade 3-4 adverse events (AEs) were neutropenia (11/24%) and anemia (3/16%), and other AEs were similar between two arms. Conclusions: The 2nd-line chemotherapy for pts with early progression in the 1st-line BEV-containing chemotherapy showed poor outcomes regardless of strategy.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7524-7524
Author(s):  
Neda Alrawashdh ◽  
Ali McBride ◽  
Daniel O. Persky ◽  
Joann Sweasy ◽  
Brian Erstad ◽  
...  

7524 Background: The survival of chronic lymphocytic leukemia (CLL) patients has progressively improved after the approval of new targeted therapy for first-line treatment and relapsed disease. We performed a corresponding analysis from the U.S. population-based SEER database (1973–2017) to explore the trend of survival and the effect of advanced CLL treatment on overall survival in CLL patients. Methods: Data were extracted from SEER*Stat for all patients 15 years or older with a primary diagnosis of CLL with or without subsequent cancers. A period analysis was performed to estimate the 5- and 10-year relative survival rates for patients diagnosed (dx) during different calendar periods from 1985 to 2017, based on gender and age at time of diagnosis (15–44, 45–54, 55–64, 65–74, 75–84, 85 years or older). A mixture cure model was used to examine the proportion of long-term survivors per gender and age category among CLL patients diagnosed between 1985 and 2015. Cox proportional hazard modeling was used to calculate the hazard ratios (HRs) of death adjusted for gender and age at diagnosis for two cohorts: (a) diagnosed in 2000–2003 and followed to 2012; (b) 2004–2007 and followed to 2015. Results: For males, the 5-year age-adjusted relative survival rate improved progressively from 72.0% (dx 1985-1989) to 88.2% (dx 2010-2014); for females, from 76.8% (dx 1985-1989) to 90.8% (dx 2010-2014). The corresponding 10-year age-adjusted relative survival rates were 47.3% (dx 1985-1989) and 72.5% (dx 2005-2009) for males; and 58.2% (dx 1985-1989) and 78.7% (dx 2005-2009) for females. The table below shows the proportions of long-term survivors for the 1985–2017 cohort as estimated in the mixed cure model. The HRs (95%CI) of death for cohort (b) in comparison to cohort (a) were 0.58 (0.43–0.78), 0.58 (0.48–0.70), 0.57 (0.49–0.67), 0.68 (0.54–0.85); and 0.83 (0.68–1.02) for age categories of 45–54, 55–64, 65–74, 75–84, and 85 years or old. Conclusions: Survival is significantly improved by calendar period among patients diagnosed after 2004 and treated in the era of advanced therapies. Females and younger patients had a higher probability of long term survival. Future studies should consider such covariates as treatment type, disease stage and genetics.[Table: see text]


2019 ◽  
Vol 53 (4) ◽  
pp. 388-396 ◽  
Author(s):  
Mojca Jensterle ◽  
Soncka Jazbinsek ◽  
Roman Bosnjak ◽  
Mara Popovic ◽  
Lorna Zadravec Zaletel ◽  
...  

Abstract Background Childhood and adult-onset craniopharyngioma is a rare embryogenic tumor of the sellar, suprasellar, and parasellar region. Survival rates are high; however, tumor location and treatment sequalae including endocrine deficits, visual impairment, metabolic complications, cognitive and psychosocial deficits can significantly impair patient’s quality of life. There is considerable controversy regarding the optimal management of craniopharyngiomas. Subtotal resection of the tumor followed by targeted irradiation to avoid further hypothalamic damage is currently indicated. Novel insights in the tumor’s molecular pathology present the possibility for targeted therapy possibly decreasing the rate and severity of treatment-associated morbidity. Conclusions Craniopharyngioma should be seen as a chronic disease. To achieve optimal outcomes a multidisciplinary team of specialized neurosurgeons, neuro-radiologists, neuro-oncologists, pathologists and endocrinologists should be involved in the diagnosis, planning of the surgery, irradiation and long-term follow-up.


1994 ◽  
Vol 17 (9) ◽  
pp. 492-498 ◽  
Author(s):  
K. Minami ◽  
H. Posival ◽  
A. El-Bynayosy ◽  
M.M. Körner ◽  
H. Schrofel ◽  
...  

Since we started using ventricular assist devices (VAD) in July 1987 up to August 1993, 63 of 15,650 (0.4%) patients (pts) who underwent open heart sugery were supported postoperatively by VAD at out institution. Forty-three were male and 20 female, mean age 55.5 years. In 49 pts coronary artery bypass grafting (CABG), in 8 pts valve surgery, in 3 pts combined CABG and valve surgery and in 3 pts corrective procedures for congenital heart disease were performed. Perioperative myocardial infarction was the most frequent indication (73%). In 37 of the 63 pts (58.7%) a centrifugal (Biomedicus pump (group A) was used and in 26 pts (41.3%) a pulsatile Abiomed BVS 5000 (group B). Fourteen of 37 pts (38%) in group A were weaned from the VAD and all of them were discharged. Twenty-three pts were unable to be weaned and 19 of these pts died. The remaining 4 pts were transplanted successfully and subsequently 3 died and 1 was discharged. In all, 15 pts (39%) were long-term survivors. Sixteen of 26 pts (62%) in group B were weaned from VAD and 13 (50%) of them were discharged of whom 3 died. Ten patients were unable to be weaned and 7 of these died. The remaining 3 pts were transplanted successfully. In all, 16 pts (61.5%) were long-term survivors. The shorter the interval between beginning resuscitation and application of VAD the better the outcome. Younger age, VAD installation in OR, support time between 2 and 7 days and Abiomed pump, influence the survival rate positively. Because of higher recovery and survival rates in patients assisted by Abiomed compared to the Biomedicus pump, we recommend the Abiomed pump in postcardiotomy cardiac failure.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15112-e15112
Author(s):  
Sevil E. Bavbek ◽  
Zafar I Malik ◽  
Giuseppe Di Lorenzo ◽  
Hans-Jorg Scholz ◽  
Inge M van Oort ◽  
...  

e15112 Background: In the TROPIC trial (NCT00417079), treatment with CbzP produced a statistically significant improvement in overall survival vs mitoxantrone + prednisone (MP) in patients (pts) with mCRPC previously treated with a docetaxel (D)-containing regimen (HR 0.70; p< 0.0001). These results supported the establishment of 2 programs (based on local regulations): a compassionate use (CUP) and an early access program (EAP; NCT01254279). Methods: The aims of the CUP/EAP are to provide drug to pts with mCRPC who may benefit from CbzP prior to commercial availability and further assess CbzP safety profile. Total enrollment for both programs is estimated at 1600 pts from 250 centers globally. Eligible pts receive CbzP (25 mg/m2 Q3W + prednisone 10 mg PO QD) until disease progression, death, unacceptable toxicity or physician/pt decision. Results: Baseline characteristics and safety data are available for the first 399 pts: median age was 68 yrs (range 43–89), with 90.2% ECOG PS 0–1. The median cumulative dose of prior D was 675 mg/m2; prior therapy with MP was permitted. For pts whose disease progressed following D, median time from last dose of D to progression was 4 months; 53.3% of pts experienced disease progression either during or < 3 months after D. 61% of pts had ≥ 2 metastatic sites; the most common were bone (93.2%) and regional lymph nodes (34.4%). At the time of analysis, a median of 4 cycles of CbzP had been administered; 4 pts received ≥ 10 cycles. Median relative dose intensity was 99.2% (range 80.1–104.9). G-CSF was administered to 34.3% of pts in Cycle 1 (6.3% therapeutic, 26.6% prophylactic). Overall, 71.4% of pts had adverse events (AEs; all grades). Most common grade 3-4 AEs were neutropenia 11.3%, febrile neutropenia 6.3%, anemia 2.8%, fatigue 2%, neutropenic sepsis 1.8%, vomiting 1.3% and diarrhea 1%. Eight (2%) treatment-related deaths were reported. Conclusions: The CUP/EAP provides additional safety data for CbzP in a routine clinical practice pt population with heavily pre-treated mCRPC. Treatment with CbzP was tolerable, with a predictable and manageable toxicity profile consistent with data reported for TROPIC and the product labeling.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3056-3056
Author(s):  
Chang Xia ◽  
Douglas Earl Laux ◽  
Jeremy Michael Deutsch ◽  
Melanie Frees ◽  
Brian Smith ◽  
...  

3056 Background: Epigenetic gene regulation is likely a contributing mechanism of cancer initiation and progression. Emerging evidence indicates that epigenetics may also play a key role in the development of chemoresistance in melanoma. We proposed combining the histone deacetylase inhibitor panobinostat (PT) and the demethylator decitabine (D) to overcome the development of epigenetic mediated temozolomide (TMZ) resistance in metastatic melanoma. Methods: Eligible patients must be ≥18, stage IV melanoma, and naïve or previously treated, with good performance status (ECOG ≤ 2) and normal organ functions. Patients with previous exposure to TMZ were allowed on study. The study includes the dose escalation of D and PT followed by expansion cohorts. D (0.1mg/kg SQ, 0.2mg/kg SQ) on days 1, 3, 5, 8, 10,12, PT (10mg PO, 20mg PO, 30mg PO) Q96h starting day 8, and TMZ 150mg/m2 PO daily on days 9-13 of each 42 day cycle. TMZ was increased to 200mg/m2 in the absence of grade 2 thrombocytopenia. Primary endpoints of phase I study are to determine the toxicity, safety and maximum tolerated dose (MTD) of the D, PT and TMZ combination. Results: To date, the phase I portion of this trial is completed. We report on the safety data for this combination. 17 patients received treatment (1st cohort: 5; 2nd cohort: 4; 3rd cohort: 4; 4th cohort: 4 ). M:F 11:6. Median age: 56 (32-77); Median ECOG PS: 1; 82% of the patients received at least one cycle (n=14). Median number of cycles given: 2 (0-6). To date, no DLTs have occurred. The MTD was not reached. The only grade (G) 4 adverse event (AE) is neutropenia on a patient in cohort 3 and it resolved within 3 days. G3 AEs included lymphopenia (n=4, 23%), anemia (n=2, 12%), leukopenia (n=2, 12%) and fatigue (n=2, 12%). Common G2 toxicities were leukopenia (n=5, 30%), neutropenia (n=4, 23%), nausea (n=4, 23%) and lymphopenia (n=3, 18%). Conclusions: The combination of D, PT, and TMZ appears to be safe and well-tolerated. The recommended dose for the phase II study remains to be determined.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 253-253 ◽  
Author(s):  
Sergio Bracarda ◽  
Giuseppe Di Lorenzo ◽  
Donatello Gasparro ◽  
Paolo Marchetti ◽  
Francesco Boccardo ◽  
...  

253 Background: A significant number of docetaxel (D) refractory mCRPC patients (pts) have a life expectancy of > 15 months and ask for additional efficacious treatments. In the phase 3 TROPIC trial treatment of mCRPC patients with CbzP who progressed during or after docetaxel resulted in a statistically significant overall survival benefit compared with mitoxantrone / prednisone (Lancet 2010). This survival benefit supported establishment of a global early access program (EAP), allowing pts with mCRPC to have access to the drug prior to its commercial availability. Here we describe preliminary safety results from the EAP in Italy. Methods: We report here the data of the first 16 mCRPC patients (out of the 123 enrolled by 19 Italian centers until Sept 2011 in EAP) treated with Cbz (25mg/m2 Q3W) plus P(10mg bid). Results: Pts were median age 73.5 years (>75 years 38%), ECOG PS-0 81.3% and had received a median of 7 prior cycles of D (median cumulative D dose 562.5mg). Median time from last D dose to inclusion was 7.1 months. Overall, 62.5% (10 Pts) had 2 or more metastatic sites (bone 94%, regional/distant lymph nodes 25% and 44%, lung 12.5%, other sites 19%). A limited number of relevant adverse events (AE) were observed. All grade AEs were seen in 14/16 pts (81.3%), with 4/16 pts experiencing grade 3/4 leukopenia, 8/16 pts grade 3 - 4 neutropenia, one patient with febrile neutropenia and one with hypertransaminasaemia. Grade 1-2 asthenia and fatigue were experienced respectively by 2 pts. No grade 3 / 4 diarrhea, vomiting or constipation were observed and no AEs results in death. All pts received at least 2 cycles of CbzP (2÷5) and only one patient permanently discontinued treatment (disease progression). Conclusions: This preliminary analysis of Italian pts enrolled in the EAP provides real world safety data and suggests a good safety profile of cabazitaxel even in heavily pretreated pts, which is in agreement with Italian experience in TROPIC. Results of the entire Italian cohort with a longer follow-up will be presented.


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