Concurrent Paclitaxel and Radiation in the Treatment of Locally Advanced Head and Neck Cancer

2001 ◽  
Vol 19 (3) ◽  
pp. 800-811 ◽  
Author(s):  
John B. Sunwoo ◽  
Laurie L. Herscher ◽  
Glenn S. Kroog ◽  
Giovana R. Thomas ◽  
Frank G. Ondrey ◽  
...  

PURPOSE: To determine the feasibility of an organ preservation regimen consisting of infusional paclitaxel administered concurrently with radiotherapy to patients with locally advanced head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Thirty-three previously untreated patients with stage III or IV tumors were enrolled onto the study. Paclitaxel was administered as a 120-hour continuous infusion every 3 weeks during the course of radiation therapy. Sixteen patients received a paclitaxel dose of 105 mg/m2, and 17 patients received 120 mg/m2. Radiation was delivered in a standard format at 1.8 Gy/d to a total dose of 70.2 to 72 Gy. RESULTS: Three months after therapy, a 76% complete response (CR) at the primary site and a 70% overall CR was achieved. At 36 months, locoregional control was 55.7%, overall survival was 57.8%, and disease-free survival was 51.1%. The median survival duration for all 33 patients was greater than 50 months at the time of this report. Local toxicities including mucositis, dysphagia, and skin reactions were severe but tolerable. All patients retained functional speech, and all but four patients were swallowing food 3 months after treatment. Steady-state plasma concentrations for paclitaxel were not achieved during a 120-hour infusion, suggesting a nonlinear process. Tumor volume quantified by pretreatment computerized tomography imaging was associated with likelihood of response and survival. CONCLUSION: Paclitaxel administered as a 120-hour continuous infusion in combination with radiotherapy is a feasible and promising treatment for patients with advanced HNSCC.

1990 ◽  
Vol 8 (2) ◽  
pp. 241-247 ◽  
Author(s):  
E E Vokes ◽  
R L Schilsky ◽  
R R Weichselbaum ◽  
M F Kozloff ◽  
W R Panje

Both cisplatin and leucovorin (LV) interact with fluorouracil (5-FU) by increasing intracellular reduced folate levels and thereby the inhibition of thymidylate synthase. Therefore, the addition of LV to cisplatin and 5-FU (PFL) may increase the activity of that combination in head and neck cancer. We treated 31 patients with locally advanced head and neck cancer with two cycles of neoadjuvant PFL consisting of 100 mg/m2 of cisplatin on day 1 followed by a 5-day continuous infusion of 5-FU at 1,000 mg/m2/day and oral LV at 100 mg administered every 4 hours during the entire duration of chemotherapy infusion. Two patients died during neoadjuvant chemotherapy of sudden death and sepsis, respectively, and were not evaluated for response. Of 29 evaluable patients, nine had a complete response (CR), 17 had a partial response (PR), and three had stable disease. Toxicities consisted of mild to moderate myelosuppression and moderate to severe mucositis, necessitating reduction of 5-FU on cycle 2 to less than or equal to 80% of the intended dose in 22 of 29 patients. Administration of LV by repeated oral dosing resulted in total reduced folate plasma concentrations of 5.3 (+/- 2.9) and 6.7 (+/- 3.4) mumol on days 2 and 4 of the 5-FU infusion. The sum of 1-LV and its metabolite 5-CH3-tetrahydrofolate exceeded the concentration of d-LV, consistent with selective absorption of the biologically active 1-stereoisomer from the gastrointestinal tract.


Author(s):  
Himadri Kumar Daru ◽  
Yumkhaibam Sobita Devi ◽  
Yumkhaibam Sobita Devi ◽  
Jaichand Singh ◽  
Jaichand Singh

Background: The purpose of this study was to compare the role of concomitant chemoradiation using paclitaxel versus cisplatin in locally advanced head and neck cancers.Methods: 52 patients were randomly assigned to one of the two concomitant chemoradiation arms: arm I (n=26) and arm II (n= 26) who received injection of paclitaxel 40 mg/m2 I/V 1-hour infusion before radiation, repeated weekly for 6 cycles, and cisplatin 30 mg/m2 I/V 1-hour infusion before radiation, repeated weekly for 6 cycles, respectively. The planned radiotherapy dose was 66-70 Gy, 2 Gy/day, 5#/Week in 6-7 weeks.Results: Response rates were 69.2% and 57.7% in arm I and arm II, respectively. There was no statistically significant difference observed between the study group and the control group (P = 0.85) On median follow up of 7-15 months, Disease free survival was (83.3%) in arm I compared with (73.3%) in arm II but the difference was statistically insignificant. Local toxicities including mucositis, dysphasia and skin reactions were more in the study the haematological toxicity was generally mild. On the contrary, non-hematologic toxicities were severe. Grade IV mucositis occurred in 26.9% in arm I and in 3.8% in arm II (P = 0.003). Moreover, grade IV dermatitis were encountered in 23.1% in arm I (P = 0.00).Conclusions: Both concomitant chemoradiotherapy regimens were easily given in the outpatient clinic. The regimen based on paclitaxel was more effective; however, the difference was insignificant. 


1991 ◽  
Vol 9 (8) ◽  
pp. 1376-1384 ◽  
Author(s):  
E E Vokes ◽  
R Mick ◽  
E P Lester ◽  
W R Panje ◽  
R R Weichselbaum

Fifty-one patients with locally advanced head and neck cancer were treated with three cycles of cisplatin at 100 mg/m2 followed by 5-day continuous infusion fluorouracil (5-FU) at 1,000 mg/m2/d as induction chemotherapy. Subsequent local therapy consisted of surgery for patients with resectable disease and/or radiotherapy. Three cycles of adjuvant chemotherapy were administered to patients with partial response (PR) or complete response (CR) to induction chemotherapy. Twenty-two patients (43%) had a clinical CR that was pathologically confirmed in 12 patients (24%), and 24 patients (47%) had a PR for an overall response rate of 90%. Local therapy included surgery in 24 patients (47%) and radiotherapy alone in 22 patients (43%). Adjuvant chemotherapy was administered to 32 patients (63%) frequently at great dose reduction. At a median follow-up of 90 months, the median survival is 22 months (95% confidence interval, 15 to 36 months), and the 5-year survival is 25%, with only five patients known to be alive and disease-free at this time. The median time to progression is 14 months, with 29 patients (57%) having documented progression of their head and neck cancer and eight (16%) having progression of a second neoplasm. Seven patients died of intervening medical events. This high incidence of second malignancies supports the continued investigation of chemoprevention for patients in CR. Despite the known high response rates achieved with cisplatin and 5-FU induction chemotherapy, the overall poor survival data reported here should lead to a thorough reexamination of the frequent administration of this regimen in the community.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16500-16500
Author(s):  
C. J. Calfa ◽  
M. Escalon ◽  
S. Zafar ◽  
E. Lopez ◽  
V. Patel ◽  
...  

16500 Background: Self identified racial groups share an unequal burden of head and neck cancer . Recent evidence suggests that outcome among races is different and the causes are multifactorial. Nonetheless, differences among ethnic groups have not been reported. Herein, we decided to analyze differences in treatment response and outcome among our white and Hispanic patient population treated for locally advanced head and neck cancer. Methods: Patients were identified using the tumor registry. We reviewed retrospectively the data from medical records. 100 white Hispanics (WH) and 50 white non-Hispanics (WNH) diagnosed with locally advanced head and neck cancer and treated at our institution from 2004 to 2005, were eligible for the study. Standard statistical analysis, including Kaplan-Meier survival curve and Cox proportional hazard models were used. P value of <0.05 was considered for statistical significance. Results: Preliminary results reveal that, in our study population, median age at diagnosis, gender, performance status (ECOG 0–2) and squamous cell histology did not differ significantly between the two groups. Stage 4 at diagnosis was more commonly observed in Hispanics as opposed to WNH (85.7% vs 68.6%) (P = 0.1). Surgery was more commonly used as an initial treatment option in Hispanics than WNH (42.8% vs 28.6%) (P = 0.18) while chemotherapy was less likely to be used (78.6% vs. 91.4%) (P = 0.15). Hispanics were more likely to smoke than WNH (P = 0.0003) and were equally exposed to chronic alcohol use. Patients from the Hispanic group were more likely to respond to therapy than whites by Chi-squared analysis but this difference was not statistically significant (P = 0.09). No differences were seen in disease free survival. Kaplan-Meier estimate of median overall survival was 16 months for Hispanics vs. 25 months for whites but this difference did not reach statistical significance (P = 0.26). Final analysis will be available at the time of the annual meeting. Conclusion: In our experience, a trend for decrease overall survival was noted in the Hispanic ethnic group. This may be in part due to more advanced stage at presentation. Nonetheless, in order to definitively answer this question, further research is warranted. No significant financial relationships to disclose.


2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Amit Bahl ◽  
Arun Singh Oinam ◽  
Arun Elangovan ◽  
Satinder Kaur ◽  
Gaurav Trivedi ◽  
...  

Objectives. Locoregional recurrence is the predominant pattern of treatment failure in advanced head and neck cancers. Reirradiation is a useful modality to treat inoperable head and neck cancer patients with recurrent disease. The aim of the present study was to analyze the treatment toxicity and early clinical outcomes in patients undergoing reirradiation. Methods. Twenty patients of head and neck cancers with recurrences or second cancers were evaluated. Reirradiation was done using simultaneous integrated boost volumetric modulated arc therapy (SIB VMAT), intensity modulated radiotherapy (IMRT), or conventional radiotherapy using 6MV photons. Dose prescription ranged from 30 to 60 Gy in conventional fractionation. Results. Seventeen males and three females were evaluated in this analysis. The median age of patients under study was 56.5 years. At time of analysis 8 patients (40%) had a complete response, 7 patients (35%) had progressive disease, and 25% had partial response or stable disease. Grade III-IV mucositis, dermatitis, xerostomia, dysphagia, and trismus were seen in 20%, 20%, 50%, 35%, and 45% patients, respectively, during retreatment. Patients receiving a radiotherapy dose less than 45 Gy showed a higher incidence of progressive disease (p=0.01). The median disease-free survival for patients receiving reirradiation dose of ≥46 Gy was 19±3.3 months (median ± S Error) compared to 8±2.61 months for those with a dose prescription less than 45 Gy (p=0.03). At 18-month follow-up 26% of patients undergoing reirradiation were disease-free. Conclusions. Our results show improved tumor control using a prescription of doses ≥46 Gy in retreatment setting.


2005 ◽  
Vol 23 (34) ◽  
pp. 8636-8645 ◽  
Author(s):  
Ricardo Hitt ◽  
Antonio López-Pousa ◽  
Javier Martínez-Trufero ◽  
Vicente Escrig ◽  
Joan Carles ◽  
...  

Purpose To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel, cisplatin, and fluorouracil (FU; PCF) versus standard cisplatin and FU (CF), both followed by chemoradiotherapy (CRT), in locally advanced head and neck cancer (HNC). Patients and Methods Eligibility criteria included biopsy-proven, previously untreated, stage III or IV locally advanced HNC. Patients received either CF (cisplatin 100 mg/m2 on day 1 plus FU 1,000 mg/m2 continuous infusion on days 1 through 5) or PCF (paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 on day 2, and FU 500 mg/m2 continuous infusion on days 2 through 6); both regimens were administered for three cycles every 21 days. Patients with complete response (CR) or partial response of greater than 80% in primary tumor received additional CRT (cisplatin 100 mg/m2 on days 1, 22, and 43 plus 70 Gy). Results A total of 382 eligible patients were randomly assigned to CF (n = 193) or PCF (n = 189). The CR rate was 14% in the CF arm v 33% in the PCF arm (P < .001). Median time to treatment failure was 12 months in the CF arm compared with 20 months in the PCF arm (log-rank test, P = .006; Tarone-Ware, P = .003). PCF patients had a trend to longer overall survival (OS; 37 months in CF arm v 43 months in PCF arm; log-rank test, P = .06; Tarone-Ware, P = .03). This difference was more evident in patients with unresectable disease (OS: 26 months in CF arm v 36 months in PCF arm; log-rank test, P = .04; Tarone-Ware, P = .03). CF patients had a higher occurrence of grade 2 to 4 mucositis than PCF patients (53% v 16%, respectively; P < .001). Conclusion Induction chemotherapy with PCF was better tolerated and resulted in a higher CR rate than CF. However, new trials that compare induction chemotherapy plus CRT versus CRT alone are needed to better define the role of neoadjuvant treatment.


2021 ◽  
Vol 10 (28) ◽  
pp. 2094-2098
Author(s):  
Ravisankar Thommanparambil Raveendran ◽  
Shehna Abdul Khader ◽  
Ajith Kumar Vilasini Raghavan ◽  
Jayaraman Madambath Balan ◽  
Krishnannair Lalithamma Jayakumar

BACKGROUND Concurrent chemotherapy is a well-established treatment modality for locally advanced head and neck cancer. The concept of concurrent chemotherapy and radiation was introduced in an attempt to improve the local control and possibly influence the survival because of the high rate of local and distant failures observed with the combination of surgery and postoperative radiation. The relevance of this study was to assess the efficacy of our treatment and patience compliance and also study the effect in patients treated with cisplatin based concurrent chemo radiotherapy in advanced head and neck cancer. METHODS The prospective study was conducted in the Department of Radiotherapy, Government Medical college, Thrissur, Kerala comprising the newly diagnosed patients with locally advanced head & neck cancers over one year. Conventional radiotherapy with a dose of 66 Gy in 33 fractions over 6.5 weeks was given concurrently with Inj cisplatin 100 mg / 2 IV every 3 weeks and periodically followed up for one year. RESULTS This study revealed that complete response rate was higher in 61 – 70 year age group compared to lower age groups. Complete response cases were slightly higher in T1 disease compared to higher stages. Regarding nodal status, complete response and DFS were more in N0 tumours and worst in N3 tumours. It was found that complete response rates were slightly higher in stage III than stage IV. Comparing the grade of the tumour, complete response cases were slightly higher in WD and MD compared to PD. Complete response rate and disease free survival (DFS) were slightly higher in cases who had more than two chemotherapy cycles compared to one cycle. CONCLUSIONS Concurrent chemo radiation was not well tolerated in our study group. Only 23.5 % patients were able to complete the planned treatment. The positive side was that complete response was found in about 79.4 % of study patients & DFS at one year was 80 %. KEY WORDS Concurrent Chemo Radiation, Head and Neck Cancer, Cisplatin


2018 ◽  
Vol 18 (1) ◽  
pp. 21-25 ◽  
Author(s):  
Sandeep Muzumder ◽  
Nirmala Srikantia ◽  
Ganesha Dev Vashishta ◽  
Avinash H. Udayashankar ◽  
John Michael Raj ◽  
...  

AbstractAimWeekly low-dose cisplatin is routinely used in concurrent chemoradiation (CCRT) in locally advanced head and neck cancer (LAHNC), despite 3-weekly cisplatin being the standard of care. We compared compliance, toxicity and efficacy in weekly versus 3-weekly cisplatin CCRT in LAHNC.Materials and methodsIn this retrospective study, weekly cisplatin 50 mg flat dose was compared with 3-weekly cisplatin 100 mg/m2, when given in CCRT in LAHNC with curative intent. The study outcome was compliance, toxicity, loco-regional control (LRC), disease-free survival (DFS) and overall survival (OS).ResultsEighty-four patients received CCRT from January 2013 to June 2017, 40 in weekly and 44 in 3-weekly arm. There was no difference between the arms not completing scheduled radiation therapy or chemotherapy. Patient receiving 200 mg/m2 cisplatin is higher in 3-weekly arm compared with weekly arm (75 versus 40·9%; p<0·0015). Compared with 3-weekly arm, more patient in weekly arm developed grade ≥3 mucositis (52·5 versus 15·9%, p=0·0004), day care intravenous hydration (82·5 versus 38·6% <0·0001) and in-patient admission (55·0 versus 18·2%; p=0·0004). The 2-year LRC, DFS and OS in weekly versus 3-weekly arm were: 70 versus 61·4% (p=0·406); 67·5 versus 56·8% (p=0·314); 67·5 versus 61·4% (p=0·558), respectively. The median time to LRR, DFs and OS was not reached.ConclusionsWeekly cisplatin is comparable with 3-weekly cisplatin in terms of compliance, disease control and survival, but with increased grade 3 mucositis and higher admissions for supportive care.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 6560-6560
Author(s):  
Abhishek Mahajan ◽  
Ankur Chand ◽  
Vijay Maruti Patil ◽  
Vanita Noronha ◽  
Amit Joshi ◽  
...  

6560 Background: As per the AJCC 8th edition ENE/ECS is the most important predictor for N staging of HNSCC and is one of the key predictor of outcomes. Because ENE/ECS is based on pathological findings after surgery and it is difficult to predict outcomes for locally advanced squamous head and neck cancer (LASHNC) treated radically with CCRT. We hypothesized that ENE assessed by CT imaging (rENE) may directly correlate with outcomes in LASHNC treated radically with CCRT. Methods: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with LASHNC who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT). 536 patients were accrued,182 were excluded due to non-availability DICOM CT scan, 354 patients were analysed for rENE (based on 6 criterion for metastasis and 3 for rENE). Near equal distribution of patients was achieved in CRT arm (170 patients) and NCRT arm (184 patients). There were 181 (51.1%) oropharynx and 173(48.9%) larynx and hypopharynx patients. We evaluated association of radiological ENE and clinical outcomes.The endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). Results: There were 244(68.9%) patients with radiologically metastatic nodes, out of which 140(57.3%) had rENE. There was no significant association between rENE and CRT (p value 0.3) or NCRT (p value 0.412). The median follow-up was 33.0 months (95%CI 30.7-35.2 months). Complete response was achieved in 204 (57.6%) cases, PR/SD in 126(35.6%) cases and PD in 24(6.8%) cases. rENE positive patients had poor overall 3-year survival (46.7%), poor DFS (48.8%) and LRC (39.9%) than rENE negative cases (63.6%, 87%, 60.4%). rENE positive cases had 1.71 times increase chances of incomplete response than rENE negative cases. Overall stage, clinical positive node, response, rENE and site were the only significant factors for predicting OS, DFS and LRC. Conclusions: In conclusion, pre-treatment rENE can be regarded as an independent prognostic factor for survival (OS, DFS, LRC) in patients with LASHNC treated radically with CCRT. Pre-treatment rENE is not only associated with CCRT response but is also associated with poor prognosis and hence rENE, as an imaging biomarker, can stratify responder’s vs non-responders. Clinical trial information: CTRI/2014/09/004980 .


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