Effectiveness of combined induction chemotherapy and radiotherapy in advanced nasopharyngeal carcinoma.

1993 ◽  
Vol 11 (10) ◽  
pp. 1919-1928 ◽  
Author(s):  
I W Dimery ◽  
L J Peters ◽  
H Goepfert ◽  
W H Morrison ◽  
R M Byers ◽  
...  

PURPOSE This prospective trial was conducted with the goal of achieving an improvement in both overall and progression-free survival in previously untreated patients with stage IV nasopharyngeal carcinoma who received an induction chemotherapy regimen of fluorouracil (5-FU) and cisplatin followed by radiotherapy. PATIENTS AND METHODS From January 1985 to January 1990, 47 patients with T1-4N2-3M0 squamous cell carcinoma of the nasopharynx were treated at The University of Texas M.D. Anderson Cancer Center with two to three cycles of 5-FU (1,000 mg/m2 continuous infusion per day x 5 days) plus cisplatin (100 mg/m2 continuous infusion on day 1 only) followed by radiotherapy using the conventional time/dose schedule. RESULTS The response rate to chemotherapy was 93.2% (20.5% complete response [CR]; 72.7% partial response [PR]), and the overall CR rate after radiotherapy was 86%. With a median follow-up period of 53 months, the 2-, 4-, and 6-year survival rates were 80%, 71.6%, and 67.4%; the overall treatment failure rate was 27%. Treatment was well tolerated and without significant acute or chronic toxic effects. CONCLUSION The results of this prospective study demonstrate that 5-FU plus cisplatin followed by radiotherapy can induce a durable remission in a high proportion of patients with poor-prognosis stage IV nasopharyngeal carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15159-e15159
Author(s):  
Hiroaki Iwase ◽  
Masaaki Shimada ◽  
Tomoyuki Tsuzuki ◽  
Noboru Hirashima ◽  
Masayuki Okeya ◽  
...  

e15159 Background: Carcinoma of the advanced cervical esophagus is a highly virulent disease. Although surgery is considered the standard therapy, the results of surgery alone remain poor. The present study analyzes the efficacy of concurrent chemoradiotherapy (CCRT) with S-1 and cisplatin for advanced cervical esophageal carcinoma (ACEC). Methods: CCRT comprised two courses, 30-Gy radiotherapy over 3 weeks (2 Gy per fraction, 5 times a week) accompanied by daily oral S-1 powder (80 mg/m2/day) for 2 weeks and a 24-hr cisplatin infusion (70 mg/m2) on Day 8. An identical course was administered after a 2-week break. Responders received a 5-week cycle of chemotherapy with S-1 and cisplatin. Results: Twenty-one subjects, 3 with Stage II, 14 with Stage III, and 4 with Stage IV ACEC participated, and all completed the CCRT courses. Eighteen subjects received a total of 59 cycles of chemotherapy after CCRT and a median of 3 cycles per subject was administered (range: 1 to 9 cycles). Complete response rates in subjects with Stage II, Stage III, and Stage IV diseases were 100%, 85.7%, and 25%, respectively, and a dysphagia-free status was found in 80.9%. The most serious toxicity was myelosuppression; Grades 3 and 4 neutropenia occurred in 33.3% and 9.5%, of subjects, respectively. Non-hematologic toxicities were moderate. The most common were Grade 2 nausea (38.0%), esophageal pain, and oral mucositis (19.0% each) and renal dysfunction (9.5%). Adverse events from the first course of CCRT resolved during the 2-week treatment break. Overall median progression-free survival was 1.5 years and the median survival time was 2.5 years. The 1- and 5-year survival rates were 75.0 and 27.7%, respectively. Conclusions: This regimen showed favorable antitumor activity, improving survival and quality of life with tolerable toxicity, and could become an alternative to conventional surgery for the treatment of ACEC.


1987 ◽  
Vol 96 (5) ◽  
pp. 608-614 ◽  
Author(s):  
John R. Clark ◽  
Rarbara G. Fallon ◽  
John T. Chaffey ◽  
Charles M. Norris ◽  
Karoly Balogh ◽  
...  

Nasopharyngeal carcinoma traditionally has been treated with radiotherapy alone. Although the probability of cure for patients with stage I and II nasopharyngeal carcinoma is high, the probability of cure for patients with stage III and IV disease is poor because of a higher rate of local-regional and distant failure. Between February 1981 and August 1986, 24 patients with previously untreated, stage IV nasopharyngeal carcinoma were treated with two to four monthly courses of cisplatin-based combination chemotherapy prior to radiotherapy. A response to induction chemotherapy was recorded in 75% of patients (29% complete response and 46% partial) prior to radiotherapy. By actuarial estimate with a median follow-up of 42 months, the 2-year failure-free survival for all patients was 57%. In conclusion, induction chemotherapy has significant activity in nasopharyngeal carcinoma. The toxicity of this approach, as well as the influence of initial histopathology and response to chemotherapy on survival, will be discussed.


2003 ◽  
Vol 21 (2) ◽  
pp. 320-326 ◽  
Author(s):  
Everett E. Vokes ◽  
Kerstin Stenson ◽  
Fred R. Rosen ◽  
Merrill S. Kies ◽  
Alfred W. Rademaker ◽  
...  

Purpose: The paclitaxel, fluorouracil, and hydroxyurea regimen of paclitaxel, infusional fluorouracil, hydroxyurea, and twice-daily radiation therapy (TFHX) administered every other week has resulted in 3-year survival rates of 60% of stage IV patients. Locoregional and distant failure rates were 13% and 23%, respectively. To reduce distant failure rates, we added a brief course of induction chemotherapy to TFHX. Patients and Methods: Sixty-nine patients received six weekly doses of carboplatin (AUC2) and paclitaxel (135 mg/m2) followed by five cycles of TFHX. Results: Ninety-six percent had stage IV disease. Response to induction chemotherapy was partial response 52% and complete response (CR) 35%. Symptomatically, there was a significant reduction in mouth and throat pain. The most common grade 3 or 4 toxicity was neutropenia (36%). Best response following completion of TFHX was CR in 83%. Toxicities of TFHX consisted of grade 3 or 4 mucositis (74% and 2%) and dermatitis (47% and 14%). At a median follow-up of 28 months, locoregional or systemic disease progression were each noted in five patients. The overall 3-year progression-free survival was 80% (95% confidence interval [CI], 71% to 90%), and the 2- and 3-year overall survival rates were 77% (95% CI, 66% to 87%) and 70% (95% CI, 59% to 82%), respectively. At 12 months, five patients were completely feeding-tube dependent. Conclusion: Administration of carboplatin and paclitaxel before TFHX chemoradiotherapy results in high response activity and may decrease distant failure rates. Overall survival, progression, and organ preservation/functional outcome data support definitive evaluation of this approach.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15508-15508
Author(s):  
A. Ponzanelli ◽  
V. Vigo ◽  
A. Bacigalupo ◽  
M. Marcenaro ◽  
M. Benasso

15508 Background: Concomitant chemo-radiotherapy is the standard treatment for advanced UNPC. Induction chemotherapy may improve the results further by enhancing both locoregional and distant control. Methods: Fifty patients with previously untreated, locoregionally advanced UNPC were initially treated with 3 courses of epidoxorubicin, 90 mg/mq, day 1 and cisplatin, 40 mg/mq, days 1 and 2, every 3 weeks. After a radiological and clinical response assessment patients underwent 3 courses of cisplatin, 20 mg/mq/day, days 1–4 and fluorouracil, 200 mg/mq/day, days 1–4, i.v. bolus, (weeks 1,4,7) alternated to 3 splits of radiation (week 2–3, 5–6, 8–9-10), with a standard fractionation, up to 70 Gy. Histology was WHO type 1 in 1 pt (2%), WHO type 2 in 10 pt (20%), WHO type 3 in 39 pts (78%). All patients had stage IV disease (UICC 1992). Results: All the patients are evaluable for toxicity and response. All but one received 3 cycles of induction chemotherapy. Toxicities from induction chemoyherapy were: 2% grade 3 or 4 mucositis, 22% grade 3 or 4 nausea/vomiting, 6% grade 3 or 4 haematological toxicity and one episode of febrile neutropenia. At the end of induction phase 12% of CRs, 84% of PRs and 4% of SD were recorded. All patients but two had the planned number of chemotherapy courses in the alternating phase and all but one received the planned radiation dose. Toxicities from alternating chemo-radiotherapy were: 28% grade 3 or 4 mucositis, 8% grade 3 or 4 nausea/vomiting, 24% grade 3 or 4 haematological toxicity with no episodes of febrile neutropenia. At the final response evaluation 86% of CRs and 14% of PRs were observed. At a median follow up of 39 months, 14% of patients had locoregional failure, 20% had distant failure and 2% both. The 4-year actuarial progression free survival and overall survival rates were 71% and 81%. Conclusions: Treatment of locoregionally advanced UNPC with induction chemotherapy followed by alternating chemo-radiotherapy is feasible and patients’ compliance is optimal. 4-year outcomes seems better than those reported with concomitant chemo-radiotherapy alone. No significant financial relationships to disclose.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7545-7545
Author(s):  
Miguel Angel A. Canales Albendea ◽  
Thomas A. Buchholz ◽  
Koji Izutsu ◽  
Takayuki Ishikawa ◽  
Laura Maria Fogliatto ◽  
...  

7545 Background: Obinutuzumab (G)-chemotherapy (chemo) has demonstrated improved progression-free survival compared with rituximab (R)-chemo in previously untreated advanced follicular lymphoma (FL). G is currently administered by IV infusion over ̃3–4 hours. A shorter duration of infusion in Cycle (C) 2 and subsequent cycles, as is standard practice with R, could improve convenience for patients (pts) and efficiency for infusion facilities. We report the primary analysis of the prospective, open-label, multicenter, single-arm, Phase IV, GAZELLE study (NCT03817853), which evaluated the safety of G administered as a 90-minute (min) SDI from C2 onwards in pts with FL. Methods: Pts with previously untreated FL received G (1000mg) intravenously on Day (D) 1, 8, and 15 of C1, and on D1 thereafter, plus chemo (bendamustine, CHOP, or CVP) for 6–8 cycles. In C1, pts received G at the standard infusion rate. Pts without a Grade (Gr) ≥3 infusion-related reaction (IRR) in C1 were eligible to receive G as a 90-min SDI from C2. Pts with a Gr 3 IRR in C1 received the standard G infusion in C2, and were eligible for G SDI in subsequent cycles if no Gr ≥3 IRRs occurred. Pts with a second Gr 3/4 IRR discontinued G. At the end of induction (EOI), responding pts received maintenance G (1000mg) as SDI for 2 years or until disease progression (PD). The primary endpoint was incidence of Gr ≥3 IRRs during C2. IRRs were defined as any event occurring ≤24 hours from infusion judged to be related to treatment. Secondary endpoints included adverse events (AEs) and investigator-assessed overall response rate at EOI. Results: As of December 3, 2020, 113 pts had received study treatment. Median age was 62.0 years, 50.4% were male, 61.9% had stage IV FL, and 45.1% were classified as high-risk FLIPI. Of the 110 pts who were eligible for G SDI from C2, no pt experienced a Gr ≥3 IRR with SDI in C2 (Table). One pt experienced a Gr 3 IRR with SDI in C5, presenting hypertension. All other IRRs with SDI were Gr 1/2. No Gr 4/5 IRRs were reported. Other AEs were similar to those observed in previous studies. At the clinical cut-off date, 104 pts had a CT imaging-based response assessment at EOI and 9 pts had no response assessment; 76/113 (67.3%) had a complete response, 22 (19.5%) had a partial response, and six (5.8%) had PD. Conclusions: In GAZELLE, G SDI in C2 and beyond appeared to be safe. No Gr 3 IRRs were observed in C2 and only one Gr 3 IRR was reported in subsequent cycles. The safety profile of G SDI was comparable with the established profile of G in advanced FL. Clinical trial information: NCT03817853. [Table: see text]


Author(s):  
Alice Boileve ◽  
Elise Mathy ◽  
Charles Roux ◽  
Matthieu Faron ◽  
Julien Hadoux ◽  
...  

Abstract Purpose European and French guidelines for ENSAT stage IV low tumor burden or indolent adrenocortical carcinoma (ACC) recommend combination of mitotane and locoregional treatments (LRT) in first-line. Nevertheless, the benefit of LRT combination with mitotane has never been evaluated in this selected group of patients. Methods A retrospective chart review was performed from 2003-2018 of patients with stage IV ACC with ≤2 tumoral organs who received mitotane in our center. Primary endpoint was the delay between mitotane initiation and first systemic chemotherapy. Secondary endpoints were progression-free survival (PFS) and overall survival (OS) from mitotane initiation. Adjusted analyses were performed on the main prognostic factors. Results Out of 79 included patients, 48 (61%) patients were female and median age at stage IVA diagnosis was 49.8 years (interquartile-range:38.8-60.0). Metastatic sites were mainly lungs (76%) and liver (48%). Fifty-eight (73%) patients received LRT including adrenal bed radiotherapy (14 patients, 18%), surgery (37 patients, 47%) and/or interventional radiology n(35,44%). Median time between mitotane initiation and first chemotherapy administration was 9 months (Interquartile-range:4-18). Median PFS1 (first tumor-progression) was 6.0 months (CI95%:4.5-8.6). Median OS was 46 months (CI95%:41-68). PFS1, PFS2 and OS were statistically longer in the mitotane plus LRT group compared to the mitotane-only group (Hazard ratio (HR)=0.39 (CI95%:0.22-0.68), HR=0.35 (CI95%:0.20-0.63) and HR=0.27 (CI95%:0.14-0.50) respectively). Ten (13%) patients achieved complete response, all from mitotane plus LRT group. Conclusion Our results endorse European and French guidelines for stage IV ACC with ≤2 tumor-organs and favor the combination of mitotane and LRT as first-line treatment. For the first time, a significant number of complete responses were observed. Prospective studies are expected to confirm these findings.


2021 ◽  
Vol 11 ◽  
Author(s):  
Mengshan Ni ◽  
Lijun Geng ◽  
Fangfang Kong ◽  
Chengrun Du ◽  
Ruiping Zhai ◽  
...  

ObjectiveTo analyze the therapeutic effect and prognostic factors of nasopharyngeal carcinoma (NPC) patients with distant metastases at initial diagnosis receiving induction chemotherapy with intensity-modulated radiotherapy (IMRT).MethodsA total of 129 patients who underwent platinum-based induction chemotherapy followed by definitive IMRT with or without concurrent or adjuvant chemotherapy for newly diagnosed distant metastatic NPC in our center between March 2008 and November 2018 were retrospectively analyzed. 41 patients underwent local therapy for metastatic sites. Kaplan-Meier method was used to estimate survival rates, Log-rank test and Cox proportional hazards model were used to figure out independent prognostic factors of overall survival (OS).ResultsA total of 66 patients had been dead (median follow-up time, 51.5 months). The median overall survival (OS) time was 54.2 months (range, 7-136 months), and the 1-year, 2-year, 3-year, 5-year overall survival rates were 88.0%,71.0%,58.0%, and 47.0%. Multivariate analysis found that the factors correlated with poor overall survival were pre-treatment serum lactate dehydrogenase (SLDH) >180U/L, chemotherapy cycles<4, and M1 stage subdivision (M1b, single hepatic metastasis and/or multiple metastases excluding the liver; and M1c, multiple hepatic metastases). The 5-year OS rates for M1a, M1b and M1c were 62.6%,40.4% and 0%, respectively.ConclusionPlatinum-containing induction chemotherapy combined with IMRT seemed to be advantageous to prolong survival for some NPC patients with synchronous metastases at initial diagnosis. The independent factors to prognosticate OS were pre-treatment SLDH, number of chemotherapy cycles, and M1 subcategories. Prospective clinical trials are needed to confirm the result.


2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 415-415
Author(s):  
Arish Noor ◽  
Luis E. Aguirre ◽  
Kirsten Blue ◽  
Trenton Avriett ◽  
Estrella M. Carballido ◽  
...  

415 Background: Immune checkpoint inhibitors (ICI) have been approved in solid tumors with dMMR. However, only limited data are available for PDAC with dMMR given the rarity of dMMR in PDAC. We evaluated efficacy of ICIs in PDAC with dMMR. Methods: Retrospective clinical and pathologic data were collected for patients (pts) with pancreatic adenocarcinoma from May 2017 to June 2020 at Moffitt cancer center. Results: We identified 10 pts with dMMR PDAC. The median age was 64.5 years (range: 42-86) and 4 pts were male. 4 pts had resectable disease, 3 had locally advanced and 3 had metastatic disease at initial diagnosis. MSH6 deficiency (def) was found in 2 cases, PMS2 def in 2, MLH/PMS2 def in 5, and MSH2/MSH6 in 1. 7 pts were treated with ICIs. 3 pts had locally advanced and 4 had metastatic disease when they started ICIs. 5 received Pembrolizumab (pem), 1 received ipilimumab/ nivolumab (ipi/nivo), and 1 received pem then ipi/nivo after progressive disease (PD) on pem. The median number of prior lines of chemotherapy was 1 (range 0-2). 6 pts were evaluable, and 1 had rapid disease progression after 1 dose of pem. Among 6 evaluable pts, 3 had an objective response (1: complete response and 2: partial response), and 2 had stable disease (SD). Median progression-free survival was 8.2 mo, and median overall survival was not reached with median follow-up (FU) of 6.8 mo. The median duration of response was not reached with a median FU of 22.6 mo. The pt with CR remained disease-free for up to 22 months. The pt whose treatment was switched to ipi/nivo after PD on pem achieved SD > 4mo on ipi/nivo. While on immunotherapy, one patient with ipi/nivo developed immunotherapy associated rash requiring systemic steroids, and another on pem developed hypothyroidism requiring levothyroxine. Conclusions: This series suggest ICIs can provide durable clinical efficacy in pts with dMMR PDAC.


2020 ◽  
Vol 17 (5) ◽  
pp. 568-576
Author(s):  
Yu-Wen Wang ◽  
Sheng-Yow Ho ◽  
Sung-Wei Lee ◽  
Chia-Chun Chen ◽  
Shieh Litsu ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
F. G. M. Verspoor ◽  
M. J. L. Mastboom ◽  
G. Hannink ◽  
R. G. Maki ◽  
A. Wagner ◽  
...  

Abstract Tenosynovial giant cell tumors (TGCT), are rare colony stimulating factor-1(CSF-1)-driven proliferative disorders affecting joints. Diffuse-type TGCT often causes significant morbidity due to local recurrences necessitating multiple surgeries. Imatinib mesylate (IM) blocks the CSF-1 receptor. This study investigated the long term effects of IM in TGCT. We conducted an international multi-institutional retrospective study to assess the activity of IM: data was collected anonymously from individual patients with locally advanced, recurrent or metastatic TGCT. Sixty-two patients from 12 institutions across Europe, Australia and the United States were identified. Four patients with metastatic TGCT progressed rapidly on IM and were excluded for further analyses. Seventeen of 58 evaluable patients achieved complete response (CR) or partial response (PR). One- and five-year progression-free survival rates were 71% and 48%, respectively. Thirty-eight (66%) patients discontinued IM after a median of 7 (range 1–80) months. Reported adverse events in 45 (78%) patients were among other edema (48%) and fatigue (50%), mostly grade 1–2 (89%). Five patients experienced grade 3–4 toxicities. This study confirms, with additional follow-up, the efficacy of IM in TGCT. In responding cases we confirmed prolonged IM activity on TGCT symptoms even after discontinuation, but with high rates of treatment interruption and additional treatments.


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