Radiation and Concurrent Carboplatin Administration in Locally Advanced Head and Neck Cancer

1995 ◽  
Vol 81 (5) ◽  
pp. 354-358 ◽  
Author(s):  
◽  
George Fountzilas ◽  
Dimosthenis Skarlos ◽  
Angelos Nikolaou ◽  
Anna Kalogera-Fountzila ◽  
...  

Aims and Background To improve local control in patients with locally advanced inoperable head and neck cancer we administered carboplatin concurrently with radiation. Methods Thirty-nine patients entered the study. There were 35 men and 4 women with a median age of 58 years (range, 24-74) and a median performance status of 90 (range, 60-100) of the Karnofsky scale. The primary site included nasopharynx (5 patients), oropharynx (n=10), hypopharynx (n=5), larynx (n=12), oral cavity (n=2), paranasal sinuses (n=3), salivary glands (n=1) and unknown (n=1). Histology was squamous cell carcinoma in all cases. All patients were irradiated with a 60Co unit. According to the protocol, they should receive 66-70 Gy to the tumor area and 45 Gy to the tumor-free area of the neck. Carboplatin was administered at a dose of 400 mg/m2 on days 2, 22 and 42. Results Totally, 112 cycles of carboplatin were administered, of which 106 (95%) were at full dose. Median dose intensity of carboplatin actually delivered was 170 mg/m2/week (range, 57-200). All patients were irradiated, although only 30 (77%) received >66 Gy. After the completion of combined treatment, 23 (59%, 95% C.I. 42-74%) achieved a CR and 10 (26%, 95% C.I. 13-42%) a PR. Grade 3-4 myelotoxicity was noticed in 60% of the patients. Other grade 3-4 toxicities included stomatitis (13%), dysphagia (5%) and weight loss (3%). Median time to progression was 18 months (range, 2-25). Conclusions Radiation and concurrent administration of carboplatin determined a high CR rate in patients with HNC, although the superiority of this combined modality approach over radiation alone has to be proven in phase III trials.

1997 ◽  
Vol 83 (4) ◽  
pp. 735-739 ◽  
Author(s):  
George Fountzilas ◽  
Athanassios Athanassiadis ◽  
Angelos Nikolaou ◽  
Anna Kalogera-Fountzila ◽  
John Tzitzikas ◽  
...  

Aims and Background To test the feasibility of accelerated interrupted twice-daily radiation and concurrent cisplatin administration in patients with locally advanced head and neck cancer. Patients and Methods Nineteen patients with locally advanced head and neck cancer were treated with accelerated bifractionated radiation with concurrent administration of cisplatin. There were 18 men and 1 female with a median age of 60 years (range, 17–71) and median performance status of 90 (-range, 80–100). Sixteen patients (85%) presented with stage IV disease. Primary site included the nasopharynx (n = 7), oropharynx (n = 5), hypopharynx (n = 1) and larynx (n = 6). Radiation consisted of two fractions of 1.6 Gy each daily, five times weekly to a total dose of 64 Gy. Cisplatin was administered at a dose of 100 mg/m2 on days 2 and 28 of the treatment period. Results Nine patients achieved a complete response (47%; 95% CI, 25%–70%) and 5 a partial response (26%; 95% CI, 7%–46%). Grade III–IV toxicity included leukopenia (16%), mucositis (26%), dry mouth (5%), weight loss (16%) and infection (5%). After a median follow-up of 27.11 months (range, 1–33+), 9 patients have died. Median time to progression was 11 months (range, 1–32+) and median survival 25 months (range, 1–32+). Conclusions Accelerated twice-daily radiation with concurrent cisplatin is effective in locally advanced head and neck cancer and can be safely given with manageable toxicity.


1992 ◽  
Vol 10 (2) ◽  
pp. 257-263 ◽  
Author(s):  
C Jacobs ◽  
G Lyman ◽  
E Velez-García ◽  
K S Sridhar ◽  
W Knight ◽  
...  

PURPOSE To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer, we compared the efficacy and toxicity of cisplatin (CP) and fluorouracil (5-FU), alone and in combination in a phase III trial. PATIENTS AND METHODS Two hundred forty-nine patients with recurrent head and neck cancer were randomized to one of three treatments: CP (100 mg/m2) and 5-FU (1 g/m2 x 4), CP, or 5-FU every 3 weeks. RESULTS The overall response rate to the combination (32%) was superior to that of CP (17%) or 5-FU (13%) (P = .035). Response was associated with good performance status (PS) but not with primary site, site of recurrence, histology, prior irradiation, or relative dose intensity. Median time to progression was less than 2.5 months, and there was no significant difference in median survival (5.7 months) among the groups. By multivariate analysis, patients with better PS and poorly differentiated tumors had superior survival. Hematologic toxicity and alopecia were worse in the combination arm. CONCLUSION Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents, survival did not improve.


2003 ◽  
Vol 89 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Vittorio Franciosi ◽  
Marco Fumagalli ◽  
Luciana Biscari ◽  
Roberto Martinelli ◽  
Teore Ferri ◽  
...  

Background and Aims To evaluate the feasibility in clinical practice of alternating chemo-radiotherapy in locally advanced head and neck cancer patients. Patients and Methods From August 1993 to April 1998 at the Division of Medical Oncology of Parma, 48 consecutive patients were observed, and 38 (79%) started the Merlano chemo-radiotherapy. The characteristics of the patients were: males (32, 84%); median age, 57 years; PS <2 (32, 84%). The primary sites were the oropharynx (18, 47%), oral cavity (8, 21%), hypopharynx (7, 19%), larynx (5, 13%); stage IV disease was present in 29 (76%) patients. Twenty-five (66%) patients were married, and 24 (63%) resided outside of the city. Results The compliance was very low: 21 patients (55%) performed all the programmed cycles of chemotherapy, whereas only 5 patients (13%) performed the chemo-radiotherapy at full doses without any delay. The objective responses were 3 (8%) complete and 21 (55%) complete plus partial responses. Failures were 2 (5%) stable disease and 2 (5%) progressive disease, and the response was not assessable in 10 (26%). The median duration of the response was 8 months. The median overall survival and the time to progression were 18 and 13 months, respectively; the 5-year overall and relapse-free survival were 36% and 26%, respectively. Nine (24%) patients were still alive as of August 30, 2001, 8 (21%) of them without progression. Twenty-six patients (68%) died with a local-regional relapse. One patient (3%) died for a second cancer. Grade 3–4 hematologic toxicity was leukopenia (n = 25, 66%) and thrombocytopenia (n = 9, 24%); grade 3–4 non-hematologic toxicity was diarrhea (n = 3, 8%) and mucositis (n = 2, 5%). Two patients (5%) died for intestinal infarction and perforation possibly related to treatment. Conclusions Compliance to the chemo-radiotherapy was very poor. The response rate was lower than that reported in clinical trials, whereas overall survival was comparable. The alternating chemo-radiotherapy is a very complex treatment that cannot be easily applied in clinical practice; a careful selection of patients is mandatory not only considering oncologic and medical criteria, but also the level of awareness of the patient and his family.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6064-6064
Author(s):  
M. Tahara ◽  
K. Araki ◽  
N. Kiyota ◽  
S. Takeuchi ◽  
N. Fuse ◽  
...  

6064 Background: An oral fluoropyrimidine, S-1, has shown high efficacy against head and neck cancer (HNC) with a response rate of 34% and preclinical data has demonstrated a possible synergy with platinums and taxanes. The aim of this study was to determine the maximum tolerated dose (MTD) of a combination therapy with TPS in patients (pts) with locally advanced or recurrent/ metastatic HNC. Methods: The eligibility criteria were: histologically proven squamous cell carcinoma of the head and neck with recurrent/metastatic and locally advanced lesions, PS 0–1, age =75 years, adequate organ function, and no prior chemotherapy. Chemotherapy consisted of 1-hour infusion of docetaxel at escalating doses of 50 and 60 mg/m2, 2-hour infusions of cisplatin at 70 mg/m2/day on day 1 and S-1 twice daily on days 1–14 at escalating doses of 40, 60, and 80 mg/m2/day. The treatment was repeated every 4-weeks. Results: Twenty two pts were enrolled. These were 17 males and 5 females with a median age of 50 years (22–74). There were 11 locally advanced and 11 metastatic cases. Median of 3 cycles were administrated (range 1–6; total 77 cycles). Anorexia, nausea, neutropenia and anemia were the most frequently observed adverse events. Grade 3 or 4 hematological toxicities were neutropenia (59%), febrile neutropenia (0%), anemia (14%) and thrombocytopenia (0%). Although a total of 12 pts were treated with TPS at doses of 60/70/80 mg/m2/day, one-dose limiting toxicity (grade3 infection) was observed at these doses, but MTD was not reached. As the approved dose of S-1 is 80 mg/m2, further dose escalation was not conducted. In a total of 22 pts treated with the TPS, 3 (1 locally advanced, 2 metastatic cases) achieved complete response and 11 (7 locally advanced, 4 metastatic cases) achieved partial response according to RECIST with an overall response rate of 64%. Conclusions: The TPS combination was well tolerated in pts with locally advanced or recurrent/ metastatic HNC. Although MTD was not reached and the data were preliminary, the antitumor activity was very promising, and this warrants further investigation. No significant financial relationships to disclose.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6021-6021
Author(s):  
M. Tahara ◽  
K. Araki ◽  
N. Kiyota ◽  
S. Okano ◽  
N. Fuse ◽  
...  

6021 Background: An oral fluoropyrimidine, S-1, has shown high efficacy against head and neck cancer (HNC), with a response rate of 34%. We investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin and S-1 (TPS) in patients (pts) with locally advanced or recurrent/metastatic HNC. Methods: Eligibility criteria were histologically proven HNC, PS 0–1, age ≤75 years, adequate organ function, and no prior chemotherapy. Treatment consisted of 1-hour infusion of docetaxel at escalating doses of 50, 60 and 70 mg/m2, 2-hour infusion of cisplatin at 70 mg/m2/day on day 1, and S-1 twice daily on days 1–14 at escalating doses of 40, 60, and 80 mg/m2/day. This regimen was repeated every 3 or 4 weeks. Pts with locally advanced HNC received concurrent chemoradiotherapy after completion of 3 cycles of TPS. Results: Forty pts were enrolled, consisting of 33 males and 7 females with a median age of 50 years (range 22–74 years). Twenty-nine cases were locally advanced cancer and 11 were metastatic cancer. 116 cycles (median = 3, range 1–6) were administered in 6 dose levels. Grade 3 or 4 hematological toxicities were neutropenia (59%), febrile neutropenia (13%), and anemia (8%), whereas no grade 3 or 4 thrombocytopenia was seen. Two dose-limiting toxicities (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg/m2/day every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 pts treated at dose level 6 (TPS: 70/70/60 mg/m2/day every 3 weeks), three DLTs were seen, namely one grade 3 diarrhea, one grade 3 ALT/AST and one grade 2 creatinine elevation. Of a total of 40 pts, 6 achieved a complete response and 22 a partial response according to RECIST, giving an overall response rate of 70%. Conclusions: The TPS combination was well tolerated. The recommended phase II dose was determined to be TPS at 70/70/60 mg/m2/day every 3 weeks. Antitumor activity was highly promising, and warrants further investigation. No significant financial relationships to disclose.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6078-6078
Author(s):  
Nathalie Letarte ◽  
Vincent-T. Taillefer ◽  
Céline Marty ◽  
Louise Lambert ◽  
Francine Aubin ◽  
...  

6078 Background: Chemoradiotherapy used for the treatment of locally advanced head and neck cancer (HNC) causes a high incidence of mucositis that may be accentuated by a reactivation of herpes simplex virus (HSV). To date, no study has evaluated the impact of antivirals used as prophylaxis to prevent mucositis or their severity. Methods: This is a retrospective observational study including patients who received at least one cycle of concurrent chemoradiotherapy for the treatment of head and neck cancer between January 2014 and June 2017 at the Centre hospitalier de l’Université de Montréal (CHUM). HSV negative patients were excluded. After approval by the IRB, we compared the incidence and severity of mucositis in HSV positive patients who started an antiviral prophylaxis before cycle 1 or 2 (prophylaxis group) to HSV+/unknown HSV patients who did not receive antiviral prophylaxis (control group). Emergency visits and hospitalizations related to mucositis were collected. Mucositis were assessed regularly by radiation oncologists during the treatment. Results: Of 482 patients who received concurrent chemoradiotherapy for HNC, 75 were HSV negative and 407 were included in this study. In the group with (n = 94) and without prophylaxis (n = 313), patients received carboplatin and 5-FU (77% vs 62%) and cisplatin (23% vs 38%) with concurrent radiation respectively. The rate of all grade mucositis in patients with and without prophylaxis (99% vs 96%; p = 0.19) was not statistically significant. The rate of grade 3 and 4 mucositis (42% vs 49%; p = 0.29), the rate of emergency visit (29% vs 28%; p = 0.91) and hospitalization (9% vs 8%; p = 0.80) were not statistically significant between each group. However, in a subgroup of patient receiving carboplatin and 5-FU, antiviral prophylaxis seems to decrease significantly the rate of grade 3 (49% vs 63%; p = 0.04). Conclusions: The addition of antiviral prophylaxis in HSV positive in patients undergoing concurrent chemoradiotherapy for locally advanced HNC didn’t decrease the rate of all grade mucositis. In the subgroup of patients receiving carboplatin and 5-FU mainly of oropharynx origin, HSV prophylaxis decreased the severity of mucositis.


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.


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.


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