Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for locally advanced head and neck cancer: a clinical and pharmacologic analysis.

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.

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.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e17006-e17006
Author(s):  
Kenji Nakano ◽  
Yasuyoshi Sato ◽  
Yukiko Sato ◽  
Takashi Toshiyasu ◽  
Takao Asari ◽  
...  

e17006 Background: CCRT is a standard therapy for locally advanced head and neck cancer patients, but some patients have intolerance to high dose density of CDDP. Predictive factors for CDDP discontinuation need to be investigated for making appropriate treatment decisions. Methods: We retrospectively analyzed nonmetastatic head and neck cancer patients treated with CCRT with CDDP (80 mg/m2 per 3 weeks) from November 2005 to April 2012 in our institute. Radiation therapy was performed as three-dimensional radiotherapy or intensity-modified radiotherapy (IMRT). Results: A total of 164 patients received CCRT, of which 89 (54 %) were Stage IV;. Primary sites were as follows; oral cavity 7, oropharynx 52, hypopharynx 53, larynx 14, nasopharynx 30, paranasal sinus/nasal cavity 3, and unknown primary 5. IMRT was performed to 54 (33 %) patients. Median follow-up time was 19 months (range 1-69 months); 1-year overall survival (OS) and progression free survival (PFS) were 90 % and 78 %. Non-Stage IV; and high creatinine clearance (>70 ml/min) were associated with longer OS in Cox proportional hazard model. As for CDDP treatment, 75 (46 %) patients completed 3 cycles of CDDP, 69 (42 %) patients received 2 cycles, and 20 (12 %) patients received only 1 cycle. The main reasons for CDDP discontinuation were infection (24 patients) and renal dysfunction (18 patients). In logistic regression analysis, male sex, younger age (< 61 years) and high body mass index (BMI) (>25) were associated with 3 cycles completion of CDDP statistically significantly (p = .002, odds ratio 6.622; p = .006, odds ratio 2.602; p = .035, odds ratio 2.655, respectively). Conclusions: In CCRT to head and neck cancer patients, infection and renal dysfunction were the main reasons for CDDP discontinuation. Sex, age and BMI could be predictive of CDDP completion/discontinuation.


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


2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 6056-6056
Author(s):  
Chantal Driessen ◽  
Maike Uijen ◽  
Winette T.A. Van Der Graaf ◽  
J. H. Kaanders ◽  
Tom Nijenhuis ◽  
...  

2021 ◽  
pp. 79-81
Author(s):  
Swapan Kumar Mallick ◽  
Rinki Saha

Introduction: Head and neck cancer is the commonest malignancy in India. Most of the cases present are at a locally advanced stage. Concurrent chemo radiotherapy is one of the treatment options in locally advanced Head & Neck Cancer patients. Materials & Methods: Locally advanced head and neck cancer patients attending the Out Patient Department of Radiotherapy from May 2018 to February 2020. Patients were treated with concurrent chemoradiation and followed for a minimum period of 9 months. Results: On analysing the pattern of response, it was noted that, in the chemoradiation complete response was seen in 20 patients (66.66%), partial response in 6 patients (20%), stable disease in 2 patients (6.66%) and progressive disease in 1 patient (3.33%). In our study, complete Response in case of Stage III was seen in 18 patients and other form of response was seen in 3 patients . In case of Stage IV A and IV B , Complete Response in 2 patients and other form of response was in 6 patients respectively. Haematological toxicities like neutropenia (3.3%), thrombocytopenia (0%) and anaemia (3.3%) were seen. Acute toxicities like oral mucositis and skin reaction were observed 10% in both the cases. Conclusions: The present study, Concomitant chemoradiotherapy improved overall survival and locoregional control. Preservation of function is a major endpoint of interest.


Head & Neck ◽  
2015 ◽  
Vol 38 (S1) ◽  
pp. E1575-E1581 ◽  
Author(s):  
Chantal M. L. Driessen ◽  
Maike J. M. Uijen ◽  
Winette T. A. van der Graaf ◽  
Claudia C. M. van Opstal ◽  
Johannes H. A. M. Kaanders ◽  
...  

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