scholarly journals Impact of Rechallenge with Imatinib in Patients with Advanced Gastrointestinal Stromal Tumor after Failure of Imatinib and Sunitinib

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Akira Sawaki ◽  
Tatsuo Kanda ◽  
Yoshito Komatsu ◽  
Toshirou Nishida

Purpose. This retrospective, nonrandomized study investigated the effect of imatinib rechallenge plus best supportive care (BSC) on overall survival after imatinib and sunitinib treatment for patients with locally advanced or metastatic gastrointestinal stromal tumor (GIST).Methods. Twenty-six patients who had previously been exposed to both imatinib and sunitinib were enrolled in this study. The treatment regimen was BSC with or without imatinib, based on the patient’s choice after discussion with his or her physician. The primary endpoint was overall survival, and secondary endpoints were time to treatment failure, clinical response rate assessed by Choi criteria, and safety.Results. Fourteen patients were treated with imatinib plus BSC and 12 received BSC alone. Median overall survival was greatly improved for the imatinib group, although differences were not significant (22 months for imatinib plus BSC versus 4 months for BSC;P=0.058). Three patients (21%) had a clinical response in the imatinib group, and one had a clinical response in the BSC alone group. Imatinib was well tolerated.Conclusions. Rechallenge with imatinib may be associated with improvement in overall survival without deteriorating performance status in patients who failed imatinib and sunitinib. A prospective study should be considered to confirm the efficacy of rechallenge with imatinib.

2021 ◽  
pp. 030089162110276
Author(s):  
Adorni Marco ◽  
Bazzurini Luca ◽  
Lissoni Andrea Alberto ◽  
Vecchione Francesca ◽  
Negri Serena ◽  
...  

Background: Squamous cell carcinoma of the vulva is a rare malignancy that affects elderly women. About one-third of vulvar cancers are diagnosed in an advanced stage, requiring extensive surgery. Neoadjuvant chemotherapy (NACT) has been introduced to reduce local tumor burden. In this retrospective study, we analyze the efficacy and toxicity of NACT followed by radical surgery. Methods: Patients with locally advanced vulvar cancer (LAVC) treated at our institution with neoadjuvant platinum and paclitaxel-based chemotherapy ± ifosfamide followed by surgery at our institution were retrospectively identified. Results: Fourteen patients (93%) completed NACT with tolerable toxicities (G3–G4 toxicity: 30%). Thirteen patients (87%) underwent surgery. The overall clinical response rate on vulvar disease was 66% (20% complete response, 46% partial response), confirmed by histopathologic analysis, while on inguinal lymph nodes it was 69% (23% complete response, 46% partial response). At the pathologic examination, all patients had negative surgical margins. Three out of 9 patients (33%) with lesions infiltrating the urethral meatus and 4 patients out of 7 (57%) with anal involvement did not require urethral amputation or colostomy, respectively, after NACT. No severe postoperative complications were described. Overall survival at 5 years was 60%, and median overall survival was 76 months. Conclusion: NACT followed by surgery in locally advanced vulvar cancer is well tolerated and allows surgical modulation.


2014 ◽  
Vol 21 (2) ◽  
pp. 295-302 ◽  
Author(s):  
Ipek Özer-Stillman ◽  
Lauren Strand ◽  
Jane Chang ◽  
Ateesha F. Mohamed ◽  
Katherine E. Tranbarger-Freier

2008 ◽  
Vol 6 (1) ◽  
pp. 37 ◽  
Author(s):  
Wilko I Staiger ◽  
Ulrich Ronellenfitsch ◽  
Georg Kaehler ◽  
Hans Schildhaus ◽  
Antonia Dimitrakopoulou-Strauss ◽  
...  

2021 ◽  
Author(s):  
Ippei Fukada ◽  
Yoshinori Ito ◽  
Naoto Kondo ◽  
Shoichiro Ohtani ◽  
Masaya Hattori ◽  
...  

Abstract PurposeThe sequence of taxanes (T) followed by anthracyclines (A) as neoadjuvant chemotherapy (NAC) has been the standard of care for almost 20 years for locally advanced breast cancer (LABC). Sequential administration of eribulin (E) following A/T could provide a greater response rate for women with LABC.MethodsIn this single-arm, multicenter, Phase II prospective study, the patients received 4 cycles of the FEC regimen and 4 cycles of taxane. After the A/T-regimen, 4 cycles of E were administered followed by surgical resection. The primary endpoint was the clinical response rate. Eligible patients were women aged 20 years or older, with histologically confirmed invasive breast cancer, clinical Stage IIIA (T2-3 and N2 only), Stage IIIB, and Stage IIIC, HER2-negative.ResultsA preplanned interim analysis aimed to validate the trial assumptions was conducted after treatment of 20 patients and demonstrated that clinical progressive disease (cPD) rates in the E phase were significantly higher (30%) than assumed. Therefore, the Independent Data Monitoring Committee recommended stopping the study. Finally, 53 patients were enrolled, and 26 patients received the A/T/E-regimen. The overall observed clinical response rate (RR) was 73% (19/26); RRs were 77% (20/26) in the AT phase and 23% (6/26) in the E phase. Thirty percent (8/26) of patients had PD in the E phase, 6 of whom had achieved cCR/PR in the AT phase. Reported grade >3 AEs related to E were neutropenia (42%), white blood cell count decrease (27%), febrile neutropenia (7.6%), weight gain (3.8%), and weight loss (3.8%)ConclusionSequential administration of eribulin after the A/T-regimen provided no additional effect for LABC patients. Future research should continue to focus on identifying specific molecular biomarkers that can improve response rates.


2010 ◽  
Vol 56 (1) ◽  
pp. 39
Author(s):  
Jeung Eun Park ◽  
Seok-Ho Dong ◽  
Kun Hyung Cho ◽  
Jae Young Jang ◽  
Hyo-Jong Kim ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4601-4601 ◽  
Author(s):  
T. Buanes ◽  
J. Maurel ◽  
W. Liauw ◽  
M. Hebbar ◽  
J. Nemunaitis

4601 Background: A phase I/II study with GV1001, a telomerase peptide vaccine, showed a median overall survival (OS) of 8.6 months in non-resectable PC (Bernhardt SL et al, Br J Cancer. 2006;95:1474–1482). This phase III trial was conducted to determine the impact on overall survival of G monotherapy vs. GV1001 in sequential combination with G in unresectable and metastatic PC. Methods: Eligible patients (pts) had chemotherapy-naive, advanced PC and ECOG performance status 0–1. Pts were randomized 1:1 to receive arm A: G (1,000 mg/m2 30 min i.v.) weekly for 7 weeks (w), 1w off and then 3w during 4-weekly cycles, or arm B: GV1001 0.56 mg s.c. plus GM-CSF as immune adjuvant on days 1, 3, 5, 8, 15, 22, 36, then every 4 weeks. Patients who progressed clinically or radiologically during GV1001 continued on GV1001 and concomitant gemcitabine. CT scans were performed every 8 weeks. The primary end-point was OS. A sample size of 520 patients allowed the detection of a hazard ratio (HR) of 0.73 (B/A), with 2α = 0.05 and 90% power. Results: Between June 2006 and May 2008, 365 pts were enrolled (A / B; 182 / 183). The study was stopped prematurely due to a preliminary analysis with 178 events showing no survival benefit of GV1001. Pts were well balanced for baseline characteristics: male 59.3% / 62.8%; median age 61y / 61y; ECOG PS 0 34.3% / 36.7%; locally advanced 22.4% / 20.7%. As of August 2008, 238 pts (A / B : 114 / 124) had died. Median OS was 7.3 / 5.9 months (HR 0.8; 95% CI 0.6–1.0). Median progression-free survival (PFS) was 3.7 / 1.9 months (HR 0.5; 95%CI 0.4–0.7). Grade 3–4 AEs: gastrointestinal 6% / 8%, infection 5% / 5%, vascular disorders 2% / 3%, neutropenia 6% / 3%. Conclusions: GV1001 did not show efficacy in sequential combination with G in advanced PC. The advantage of G monotherapy over the sequential combination may be due to the delayed treatment with G in arm B. [Table: see text]


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 162-162 ◽  
Author(s):  
Shelize Sadrudin Khakoo ◽  
Alexandros Georgiou ◽  
Justin S. Waters

162 Background: Palliative chemotherapy for advanced gastric and gastro-oesophageal junctional (GEJ) carcinoma improves tumour related symptoms and overall survival compared to best supportive care alone. EOX has been established as one of the most effective regimens in randomised clinical trials, but produced significant toxicity. We wished to examine the tolerability of EOX in everyday practice. Methods: A retrospective search was conducted to identify patients with advanced gastric or GEJ cancer, treated at our institution with at least one cycle of first line palliative EOX between 2009 and 2012. Patient baseline characteristics, toxicities (graded according to CTCAEv.4), dose reductions, treatment interruptions and discontinuations were analysed. Results: We identified 60 patients, 83% were male, and the median age was 64 years (age range18-82 years). 85% had a baseline performance status (PS) of 1, 10% PS of 2 and 5% PS of 0. 75% had GEJ cancer and the remainder had gastric cancer. 82% were commenced on standard EOX (1250mg/m2 capecitabine, 130mg/m2 oxaliplatin and 50mg/m2). 80% of patients experienced grade 3 or worse toxicity. 27% discontinued treatment due to excessive toxicity and 37% due to progressive disease. Significant toxicities (at least grade 3) were: 28% neutropenia, 27% diarrhoea, 23% fatigue, 10% vomiting, 10% anaemia, 8% neutropenic sepsis, 8% nausea, 5% thrombocytopenia, 5% peripheral neuropathy, 3% mucositis and 3% chest pain. 47% of patients required a dose reduction of at least 1 drug. 66% of patients completed 3 cycles, 35% completed 6 cycles and 18% completed 8 cycles. The mean progression free survival for patients completing 8 cycles was 4.6 months. Conclusions: EOX improves tumour related symptoms and overall survival but the benefits are often short-lived and in some patients it is associated with unacceptable toxicity, given their limited life expectancy. More thought needs to be given to prophylactic measures and modification of the EOX regimen to improve tolerability without compromising efficacy.


2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 3-3 ◽  
Author(s):  
Patrick Oh ◽  
Minsi Zhang ◽  
Paul Brady ◽  
Ellen Yorke ◽  
Elizabeth Won ◽  
...  

3 Background: Chemoradiation is an essential tool in treatment of localized esophageal cancer. Recent data indicates that cardiac dose is an independent predictor of survival after chemoradiation for locally advanced lung cancer. However, the impact of normal tissue dose in esophageal cancer has not been well characterized. We investigated cardiac and pulmonary dose-volume histogram (DVH) metrics as potential predictors of overall survival (OS) after chemoradiation for esophageal cancer. Methods: We reviewed 453 consecutive patients with stage I-III esophageal cancer treated with definitive or preoperative chemoradiation (median dose 50.4 Gy in 28 fractions) between 2007 and 2015 at our center. Most (n = 442) received intensity-modulated radiation therapy. Radiation plans were reviewed and multiple DVH metrics for heart (max and mean dose, V5Gy, V10Gy, V20Gy, V30Gy, and V40Gy) and lung (mean dose, V5Gy, and V20Gy) were extracted for analysis. Other clinical covariates (surgery, performance status, stage, and histology) were recorded. Cox univariate (UVA) and multivariate (MVA) regression was used to analyze the association of these factors with overall survival. Results: Median follow-up for surviving patients was 28.4 months. On UVA, older age, lower performance status, Stage III disease, lack of surgery, heart V40Gy, lung V5Gy, lung V20Gy, and lung mean dose were significantly associated with decreased survival. On MVA, surgery (p = 0.008), stage III disease (p < 0.0002) and lung V20Gy (p = 0.0389) remained significant, while heart V40Gy did not (p = 0.211). Patients with lung V20Gy< 20% had a median survival of 44.0 months, compared to 24.0 months for patients with lung V20Gy≥20%. Conclusions: This comprehensive dosimetric analysis of heart and lung dose in a large cohort of esophageal cancer patients suggests that lung dose is a significant independent predictor of survival. Cardiac dose was not independently predictive after adjusting for lung dose and other clinical factors. This data suggests that esophageal cancer outcomes may be improved by minimizing lung dose, particularly the volume receiving 20Gy or more, and provides further rationale for pursuing new techniques to reduce lung dose, such as proton therapy.


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