Dose intensive chemotherapy (Cx) in advanced thymoma: Initial report of Japan Clinical Oncology Group trials (JCOG 9605 and 9606)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7080-7080
Author(s):  
H. Kunitoh ◽  
T. Tamura ◽  
H. Fukuda ◽  
K. Nakagawa ◽  
K. Takeda ◽  
...  
Keyword(s):  
Thymic Carcinoma ◽  
Local Therapy ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Initial Report ◽  
Free Survival ◽  
Unresectable Stage ◽  
Short Course ◽  
Ecog Ps

7080 Background: Thymoma is considered to be sensitive to Cx. Dose intensive Cx might well be suitable for such tumors, especially in combination with local therapy. Objectives of the trials were to evaluate the safety and efficacy of the dose intensive CODE (cisplatin[C]- vincristine[O]- doxorubicin[D]- etoposide[E]) Cx in thymoma. The primary endpoint was progression-free survival time (PFS). Methods: Patients (pts) with 15–70 years of age with histologically documented Cx-naïve thymoma with stage IVa/IVb disease (JCOG 9605) or unresectable stage III disease (JCOG 9606) were eligible. Tumors of other histology, such as thymic carcinoma, carcinoid or lymphoma were excluded; pts were to have ample organ function and ECOG PS of 0–2. Myasthenia was allowed. Signed consent form was obtained. Pts received CODE Cx of 9 weeks (w): C 25 mg/m2 Cx day 1 on each w1–9; O 1mg/m2 d1 on w1,2,4,6,8; D 40 mg/m2 d1 and E 80 mg/m2 d1,2,3 on w 1,3,5,7,9. Cx courses were supported by GCSF. Steroids were used only for antiemesis. Those with stage III disease (JCOG 9606) went on to surgery, if judged to be resectable, and post-operative radiotherapy (RT) of 48Gy; those with unresectable disease received 60Gy RT. Results: From Jul./97 to Apr./05, 53 pts were entered to the studies. Five were found ineligible because of different histology. Pt characteristics and response to the Cx were summarized in the table . Toxicity of the Cx was mainly hematologic and generally well tolerated, with no toxic death; 70% of the pts completed planned 9 weeks. Thirteen pts in JCOG 9606 (stage III) received thoracotomy; tumor was resected in 11 pts, completely in 9 (39% of enrolled pts). Pathologic CR was observed in 3. The median PFS was 9.5m for stage IV and 4.5 y for stage III diseases. Overall survival at 2 & 5 yrs were 82% & 57% for stage IV and 96% & 77% for stage III pts. Conclusions: Short-course, dose intensive Cx was active against thymoma. Although it does not seem to bring long PFS in stage IV pts, it could improve resectability in limited disease. [Table: see text] No significant financial relationships to disclose.

scholarly journals Risk tolerance in adjuvant and metastatic melanoma settings: a patient perspective study using the threshold technique

2021 ◽  
Author(s):  
Carol Mansfield ◽  
Kelley Myers ◽  
Kathleen Klein ◽  
Jeetvan Patel ◽  
Antonio Nakasato ◽  
...  
Keyword(s):  
Stage Iv ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Risk Tolerance ◽  
Stage Iii ◽  
Acceptable Risk ◽  
Treatment Benefit ◽  
Free Survival ◽  
Unresectable Stage ◽  
Melanoma Patients

Background: Adverse events (e.g., pyrexia) may affect treatment patterns and adherence. This study explored pyrexia risk tolerance among melanoma patients when treatment benefit is unknown versus known. Materials & methods: US respondents with stage III (n = 100) or stage III unresectable/stage IV melanoma (n = 125) chose between hypothetical melanoma treatments, defined by reoccurrence/progression-free survival and pyrexia risk, one resembling standard-of-care and one resembling dabrafenib + trametinib. Respondents chose first when efficacy was unknown and then when efficacy was known; pyrexia risk was varied systematically to define maximum acceptable risk. Results: Maximum acceptable risk of pyrexia was statistically significantly higher when efficacy was known versus unknown in stage III patients (85 vs 34%) and stage III unresectable/stage IV patients (66 vs 57%). Conclusion: Patients accepted higher levels of pyrexia risk when they understood treatment benefit.

Role of modern neoadjuvant chemoradiotherapy in locally advanced thymic epithelial neoplasms

2020 ◽  
pp. 030089162096798
Author(s):  
Yirui Zhai ◽  
Dazhi Chen ◽  
Yushun Gao ◽  
Zhouguang Hui ◽  
Liyan Xue ◽  
...  
Keyword(s):  
Adverse Events ◽  
Thymic Carcinoma ◽  
Locally Advanced ◽  
Survival Rates ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Epithelial Neoplasms

Purpose: To improve resectability in patients with stage III–IVA thymic epithelial neoplasms, neoadjuvant chemotherapy and radiotherapy are considered. This retrospective study aimed to investigate the efficacy and safety of neoadjuvant therapies using modern techniques in thymic epithelial neoplasms. Methods: We included 32 patients with Masaoka stage III–IV disease treated at our institution from January 2010 to December 2017. Data regarding clinicopathologic characteristics, treatment protocols, toxicities, and survival were collected. Response was evaluated according to the Response Evaluation Criteria in Solid Tumours 1.1. Survival was assessed using the Kaplan-Meier method. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Results: Neoadjuvant radiotherapy alone, chemotherapy alone, sequence chemoradiotherapy, and concurrent chemoradiotherapy were administered to 10 (31.3%), 9 (28.1%), 3 (9.4%), and 10 (31.3%) patients, respectively. Twenty-nine patients (90.6%) underwent R0 resection. The median follow-up time was 38.0 months (3.3–109.5 months). After neoadjuvant therapy, 18 patients (56.3%) achieved partial response and 14 (43.8%) had stable disease. Pathologic complete response was achieved in 6 patients (18.8%), all of whom had thymic carcinoma. The 5-year overall and progression-free survival rates were 90.9% and 67.5%, respectively. For patients with thymic carcinoma, the 5-year overall and progression-free survival rates were 80.0% and 66.2%, respectively. Grade 3 toxicities were observed in only 1 patient (leukopenia). Conclusions: For patients with primary unresectable thymic neoplasms, neoadjuvant chemoradiotherapy is an efficient and safe choice, with favorable response and survival and moderate toxicities. Patients with thymic carcinoma might benefit more from neoadjuvant therapies.

HPV and survival in patients with oropharyngeal squamous cell cancer of the head and neck (OPC) treated with induction chemotherapy followed by chemoradiotherapy (ST) versus chemoradiotherapy alone (CRT): The Dana-Farber experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5582-5582
Author(s):  
Jochen H. Lorch ◽  
Glenn Hanna ◽  
Wei Dai ◽  
Vijaya Thotakura ◽  
Vidya Nair ◽  
...  
Keyword(s):  
Cell Cancer ◽  
Stage Iv ◽  
Clinical Information ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Group Outcomes ◽  
Hpv Status ◽  
Stage Iv Disease ◽  
Versus Stage

5582 Background: HPV status is a major prognostic marker for survival in patients with OPC. We examined overall survival (OS) and progression free survival (PFS) in patients with OPC and known HPV status treated at Dana-Farber Cancer Institute with ST and CRT between 2002 and 2011. Methods: 280 patients with OPC and known HPV status were identified retrospectively and clinical information was recorded. Results: 174 patients were treated with CRT (124 HPV positive, 50 HPV negative) and 106 patients were treated with ST (77 HPV positive, 29 HPV negative). For all 280 patients, OS and PFS were significantly better for patients who were HPV positive compared to those who were HPV negative. 3 year OS was 89.1% for HPV positive (95% CI, 83.8-94.7) and 70.5% for HPV negative patients (95%CI, 59.9-83%, HR 0.37, p=0.0007). Among HPV positive patients treated with CRT, 13/124 had died at 3 years (OS 88.5%, 95%CI 81.7-95.9) while 13 deaths were recorded among 50 HPV negative patients (OS 72.2%, 95% CI 59.1-88.2, HR 0.38, p=0.011). PFS at 3 years was also significantly better for HPV positive versus HPV negative patients(81.7% vs 58.8%, HR 0.42, p=0.006). In the group treated with ST, outcomes were similar despite a higher rate of stage IV versus stage III disease compared to the group treated with CRT (100% stage IV in ST versus 77% stage IV and 23% stage III disease in CRT group). Three year OS was 89.7% for HPV positive and 68.2% in the HPV negative group (8/77 HPV pos vs 10/29 HPV neg, HR 0.33, p=0.015). PFS was borderline better for HPV positive patients (81% vs 61.7%, HR 0.48, p= 0.058). Conclusions: We present the DFCI experience treating OPC with ST and CRT for patients with known HPV status over one decade.OS and PFS were superior for HPV positive versus HPV negative patients. Outcomes were virtually identical for patients treated with CRT versus ST despite a higher rate of stage IV disease in the ST group. Outcomes for the HPV negative patients in particular were superior compared to the published literature.

Association of dynamic changes of methylated SFRP2 in ctDNA with prognosis in advanced gastric cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15051-e15051
Author(s):  
Yan Haijiao ◽  
Kele Ge ◽  
Wenyu Chen ◽  
Xizheng Mao ◽  
Xiaodong Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dynamic Change ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Suppressor Gene ◽  
Stage Iii ◽  
Dynamic Monitoring ◽  
Free Survival ◽  
Potential Biomarker

e15051 Background: Secreted frizzled-related protein 2 (SFRP2) is a tumor suppressor gene and its hyper methylation could cause its inactivation and promote cancer development. However, whether methylated SFRP2 (mSFRP2) in ctDNA could serve as prognostic biomarker for patients with gastric cancer has not been thoroughly studied. Methods: Stage III or IV gastric cancer patients treated with systemic chemotherapy in the Third Affiliated Hospital of Soochow University from 2015 to 2017 were included. The mSFRP2 before and during chemotherapy were dynamically detected from ctDNA by digital polymerase chain reaction-based technologies. Results: In total, 121 patients were enrolled, with 63 in stage III and 58 in stage IV. Baseline median mSFRP2 was higher in stage IV than stage III (64 VS 18 copies/ng, P < 0.001). In stage III GC, the top 50% mSFRP2 population had shorter median disease-free survival (DFS, 11.0 months VS NR; HR, 13.05; 95% CI, 3.05-55.95;) and overall survival (OS, 17.0 months VS NR; HR, 7.80; 95% CI, 1.81-33.60). Similar results were observed in stage IV GC that the median progression-free survival (PFS, 4.0 VS 7.0 months; HR, 2.74; 95% CI, 1.58-4.78) and OS (12.0 VS 16.0 months; HR, 3.14; 95% CI, 1.67-5.92) was shorter in patients with top 50% mSFRP2. During the dynamic monitor along treatment, elevated mSFPR2 was associated with worse PFS (5.0 VS 7.0 months; HR, 2.17; 95% CI, 1.25-3.76) and OS (12.0 VS 15.5 months; HR, 3.51; 95% CI, 1.94-6.35) in stage IV patients. Conclusions: Our study shows the association between SFRP2 methylation and its dynamic change and prognosis in patients with gastric cancer. Our results provide a potential biomarker in ctDNA for prognosis and dynamic monitoring in patients with gastric cancer.

A phase II study of YM155, a novel survivin suppressant, administered by 168 hour continuous infusion in patients with unresectable stage III or stage IV melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8538-8538 ◽  
Author(s):  
R. Gonzalez ◽  
K. Lewis ◽  
W. Samlowski ◽  
L. Cranmer ◽  
J. Catlett ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Single Agent ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Median Number ◽  
Stage Iii ◽  
Melanoma Tumor ◽  
Minor Response ◽  
Unresectable Stage

8538 Background: In cell line studies, YM155 showed markedly potent antiproliferative activity against melanoma with 50% growth inhibition (GI50) values ranging from 0.35 nM to 910 nM. In melanoma tumor-bearing mouse xenograft models, YM155 showed significant antitumor activity including regression of tumors, at doses ranging from 1 to 10 mg/kg/day. Methods: Chemotherapy naive patients with unresectable Stage III or IV melanoma were eligible. The primary endpoint was tumor response defined by RECIST criteria. Secondary endpoints included progression-free survival and toxicity. A Simon's two stage minimax design was utilized with the first stage requiring 1 response (N=27) and a total of 2 responses required at the conclusion of stage II (N=29). Patients were considered evaluable if they completed 2 cycles. YM155 was given as a 168-hour (7-day) continuous infusion every three weeks (1 cycle) at a dose of 4.8 mg/m2/day. Results: Enrollment is complete at 34 pts in order to reach 29 evaluable with treatment ongoing. Results are available for the first 26 pts. Median age was 59 y/o, (range 29 - 88) with ECOG PS of 0–1. There is one objective response of intrabdominal lymph nodes based on Investigator assessment at Cycle 2 confirmed at Cycle 4; another patient had a minor response (24% reduction) at Cycle 6 (currently at Cycle 8). Two subjects have shown stable disease after 6 cycles and remain on study. The median number of cycles is 3 (range 1 - 9). Two of 26 pts reported a grade 3 AE considered possibly related to YM155 (chest pain - nos and catheter related thrombosis). Nineteen of 26 pts have discontinued the study (18 PD, 1 withdrew consent). Conclusions: YM155 induced responses in 2 pts and was generally well tolerated. Given this encouraging response as a single agent, studies of YM155 combined with other agents are under consideration. [Table: see text]

Sex Is an Independent Prognostic Indicator for Survival and Relapse/Progression-Free Survival in Metastasized Stage III to IV Melanoma: A Pooled Analysis of Five European Organisation for Research and Treatment of Cancer Randomized Controlled Trials

2013 ◽  
Vol 31 (18) ◽  
pp. 2337-2346 ◽  
Author(s):  
Arjen Joosse ◽  
Sandra Collette ◽  
Stefan Suciu ◽  
Tamar Nijsten ◽  
Poulam M. Patel ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Metastatic Tumor ◽  
Stage Iii ◽  
Controlled Trials ◽  
Free Survival ◽  
European Organisation ◽  
Randomized Controlled ◽  
Female Advantage

Purpose To study sex differences in survival and progression in patients with stage III or IV metastatic melanoma and to compare our results with published literature. Patients and Methods Data were retrieved from three large, randomized, controlled trials of the European Organisation for Research and Treatment of Cancer in patients with stage III and two trials in patients with stage IV melanoma. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for females compared with males, adjusted for different sets of confounders for stage III and stage IV, respectively. Results In 2,734 stage III patients, females had a superior 5-year disease-specific survival (DSS) rate compared with males (51.5% v 43.3%), an adjusted HR for DSS of 0.85 (95% CI, 0.76 to 0.95), and an adjusted HR for relapse-free survival of 0.86 (95% CI, 0.77 to 0.95). In 1,306 stage IV patients, females also exhibited an advantage in DSS (2-year survival rate, 14.1% v 19.0%; adjusted HR, 0.81; 95% CI, 0.72 to 0.92) as well as for progression-free survival (adjusted HR, 0.79; 95% CI, 0.70 to 0.88). This female advantage was consistent across pre- and postmenopausal age categories and across different prognostic subgroups. However, the female advantage seems to become smaller in patients with higher metastatic tumor load. Conclusion The persistent independent female advantage, even after metastasis to lymph nodes and distant sites, contradicts theories about sex behavioral differences as an explanation for this phenomenon. A biologic sex trait seems to profoundly influence melanoma progression and survival, even in advanced disease.

Maintenance gefitinib (G) after chemoradiotherapy (CRT) in patients (pts) with unresectable stage IIIA/B non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7188-7188
Author(s):  
J. R. Gray ◽  
D. R. Spigel ◽  
J. D. Hainsworth ◽  
E. Vazquez ◽  
J. D. Peyton ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Large Cell ◽  
Research Network ◽  
Stage Iii ◽  
Stage Iiia ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Ecog Ps

7188 Background: Concurrent CRT improves outcomes for pts with unresectable stage III NSCLC compared with radiation (RT) alone. The EGFR inhibitor G benefits select pts with advanced NSCLC. This multicenter community phase II trial examined the role of CRT followed by G for pts with unresectable stage III NSCLC. Methods: Theprimary endpoint was 2-year overall survival (OS) in pts with unresectable stage IIIA/B NSCLC (effusions, N3 mediastinal nodes >4 cm excluded) treated with CRT followed by G. Induction(I) treatment (tx): docetaxel (D) 40 mg/m2 IV and gemcitabine 800 mg/m2 IV D1, 8 Q 21D × 3 cycles. Pts without progressive disease (PD) began: D 20 mg/m2 IV and carboplatin (C) AUC = 1.5 IV weekly × 6 and RT 61.2 Gy, 1.8-Gy M-F weekly × 7 (starting 1 week prior to D/C). If no PD, pts received G 250 mg PO daily × 2 years or until PD. Eligibility:measurable disease, ECOG PS 0–1, informed consent. Intent to treat analysis. Results: One-hundred three pts were enrolled from 7/03 to 4/05. Baseline features: medianage 60 years (37–79); male/female 54%/46%; ECOG PS 0/1:26%/74%; adenocarcinoma (26%), squamous (32%), large cell (28%), mixed/not specified (14%); IIIA/B (46%/54%). Grade 3/4 toxicities were limited to ≤ 8% except for neutropenia (17%, during I) - with notx-related deaths. Complete/partial responses after I were seen in 1 pt/34 pts, respectively, for an overall response rate (RR) of 34% (95% CI 26%-44%). Forty-two pts (41%) had stable disease (SD) and 12% had PD (9 pts were unevaluable.) Seventy-four pts (72%) received D/C/RT which resulted in an overall RR of 44% (95% CI 35%-54%). Fifteen percent had SD. Fifty-six pts (54%) received G for a median of 28 weeks (1–107). Median PFS and OS are 9.9 and 15 months, respectively. After a median follow-up of 19 months, actuarial 1- and 2-year progression-free survival (PFS) is 41% and 12%, respectively. 1- and 2-year OS rates are 64% and 21%, respectively. Subset analyses by smoking, gender, histology, and stage are in progress. Conclusions: Maintenance G following CRT in unresectable NSCLC does not appear to improve survival. It is possible that further analysis may suggest a role for G in selected pts. [Table: see text]

Induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone for unresectable stage III non-small cell lung cancer (NSCLC): Randomized phase III trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7528-7528 ◽  
Author(s):  
S. Kim ◽  
M. Kim ◽  
E. Choi ◽  
H. Sohn ◽  
D. Lee ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Concurrent Chemoradiotherapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Stage Iii ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Unresectable Stage ◽  
Stage Iii Nsclc ◽  
Grade 3

7528 Background: We conducted a prospective randomized phase III trial comparing induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) versus immediate CCRT to evaluate whether the addition of induction chemotherapy would result in improved survival. Methods: Patients with unresectable stage III NSCLC, ECOG PS 0–1, and weight loss up to 10% were eligible. They were randomized to receive either induction chemotherapy followed by CCRT (arm A) or immediate CCRT (arm B) after stratification for stage (T4N0–2, T1–3N3, T4N3, and stage IIIA), histology (squamous vs non-squamous), and SCLN positivity. Induction chemotherapy consisted of two cycles of gemcitabine (1,000 mg/m2 D1, D8) and cisplatin (70 mg/m2 D1) q 21days. Chemotherapy during CCRT consisted of 6 cycles of weekly paclitaxel (50 mg/m2) and cisplatin (20 mg/m2). Radiation therapy performed with hypofractionated scheme (2.2 Gy/fraction, once a day) and total dose was 66 Gy. Irradiated volume encompassed gross tumor plus 1.0 cm margin. Results: Between March 2003 and June 2006, 134 patients were enrolled. 92% of patients were male and 60% were age 60 or older. Objective tumor response was obtained in 38% after induction chemotherapy. Response rates after completion of CCRT were 72% (95% CI, 61%–83%) on arm A and 79% (95% CI, 69%–89%) on arm B. Grade 3/4 toxicities during induction chemotherapy consisted mainly of neutropenia (11%/3%). During CCRT, grade 3/4 neutropenia was noted in 8%/5% (arm A) versus in 8%/0% (arm B), grade 3 anemia was 8% vs 0%, grade 3 thrombocytopenia 5% vs 0%, and grade 3 esophagitis 16% vs 16%. At median follow-up of 28 months, median survival was 12.6 months (95% CI, 8.6–16.7 months) on arm A versus 18.2 months (95% CI, 11.7–24.8 months) on arm B (P=0.18). Two year survival estimates was 25% (15%–35%) and 43% (31%–55%), respectively. Median progression free survival was 7.5 months (95% CI, 5.6–9.4 months) on arm A and 11.6 months (95% CI, 9.6–13.6 months) on arm B (P=0.04). Conclusions: The addition of induction chemotherapy to CCRT failed to increase the survival of unresectable stage III NSCLC over immediate CCRT. Moreover, the progression free survival was inferior to immediate CCRT. No significant financial relationships to disclose.

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