Superior clinical response and survival rates with initial bolus of cisplatin and 120 hour infusion of 5-fluorouracil before definitive therapy for locally advanced head and neck cancer (original) (raw)
Related papers
Complications of 5-fluorouracil therapy in head and neck cancer patients
American Journal of Otolaryngology, 1995
MD is commonly used in chemotherapy protocols used to treat head and neck cancer patients. Cardiotoxicity associated with 5-FU is becoming recognized and reported with increasing frequency.l Because most patients with head and neck cancer have risk factors for cardiovascular disease, recognizing the potential for cardiotoxicity during 5-FU treatment protocols may be especially important. We present three cases of cardiac toxicity occurring with 5-FU administration in patients with head and neck squamous-cell carcinoma.
European Journal of Cancer, 1996
The aim of this study was to establish the feasibility of giving concomitant radiotherapy and 3 cycles of chemotherapy with cisplatin (CDDP), S-fluorouracil (5-FU) and mitomycin C (MMC) in locally advanced inoperable oropharyngeal cancer. From March 1990 to September 1993, 27 male patients (mean age 55 years) were included in this study. 3 patients (llO/o) were T2N0, 19 (70%) T3 (T3NO: n = 9, T3Nl: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4NO: n = 1, T4Nl: n = 1, T4N2: n = 2, T4N3: n = 1). All patients received conventional radiotherapy delivering 70 Gy in 35 fractions and 52 days, and three cycles of chemotherapy starting on day 1,21 and 42 with CDDP 20 mglm' and 5-FU 400 mg/m* day 1 to day 4, and MMC 10 mglm' day 1. With a mean follow-up of 34 months (17-59), 10 patients (37%) were alive and free of disease. Among the 17 other patients, 8 died of cancer. Crude locoregional control rate was 78%, and probability of local control at 1 and 2 years was 85 and SO%, respectively. One-and 2-year survival rates were 48 and 3 l%, respectively, for both overall and disease-free survival. Grade 3 or 4 mucositis occurred in 22 patients @lo/o; enteral feeding was necessary for 63%; mean weight loss was 5.7 kg. Grade >2 thrombocytopenia occurred in 11 patients (41%), grade >2 neutropenia in 8 patients (29%), grade >2 anaemia in 4 patients (15%). Febrile neutropenia or aplasia occurred in 5 patients (19%). 2 patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 1 month after treatment with grade 4 thrombocytopenia and septicaemia. In conclusion, a high complete response rate has been achieved with this concomitant chemo-and radiotherapy, but with severe digestive and haematological toxicity. Addition of MMC to 5-FU and CDDP might have been responsible for this increased toxicity. This therapeutic combination is therefore not routinely feasible. Copyright 0 1996 Elsevier Science Ltd
Head and Neck-journal for The Sciences and Specialties of The Head and Neck, 2005
Background.Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation.Induction chemotherapy with cisplatin and fluorouracil and radiotherapy is an effective alternative to surgery in patients with carcinoma of the larynx and hypopharynx who are treated for organ preservation.Methods.We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five eligible patients who were followed up between April 1999 and May 2001 were enrolled. Initially, these patients were treated with two cycles of induction chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5-fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who had a complete response to chemotherapy were treated with definitive radiotherapy; patients who had a partial response to chemotherapy were treated with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the duration of radiotherapy. Patients who had no response or progressive disease underwent surgery with postoperative radiotherapy. Patients with N2 or N3 positive lymph nodes underwent neck dissection after the treatment.We designed a protocol to evaluate the possibility of organ preservation in patients with advanced, resectable carcinoma of the larynx and hypopharynx. Forty-five eligible patients who were followed up between April 1999 and May 2001 were enrolled. Initially, these patients were treated with two cycles of induction chemotherapy consisting of cisplatin, 20 mg/m2/day on days 1 to 5, and 5-fluorouracil, 600 mg/m2/day by continuous infusion on days 1 to 5. Patients who had a complete response to chemotherapy were treated with definitive radiotherapy; patients who had a partial response to chemotherapy were treated with chemoradiotherapy. Cisplatin, 35 mg/m2/week, was introduced throughout the duration of radiotherapy. Patients who had no response or progressive disease underwent surgery with postoperative radiotherapy. Patients with N2 or N3 positive lymph nodes underwent neck dissection after the treatment.Results.The mean age was 56.6 years (range, 34–75 years). The overall response rate to induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3% partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all patients and 63.3% of surviving patients have had a preservation of the larynx or hypopharynx and remain disease free. The most common toxicities were nausea and vomiting and mucositis.The mean age was 56.6 years (range, 34–75 years). The overall response rate to induction chemotherapy was 71.1%, with a 17.8% complete response rate and 53.3% partial response rate. With a median follow-up of 13.7 months, 23 (51.1%) of all patients and 63.3% of surviving patients have had a preservation of the larynx or hypopharynx and remain disease free. The most common toxicities were nausea and vomiting and mucositis.Conclusion.Organ preservation, with multimodality treatment, may be achievable in some of the patients with resectable, advanced larynx or hypopharynx cancers without apparent compromise of survival. © 2004 Wiley Periodicals, Inc. Head Neck27: 15–21, 2005Organ preservation, with multimodality treatment, may be achievable in some of the patients with resectable, advanced larynx or hypopharynx cancers without apparent compromise of survival. © 2004 Wiley Periodicals, Inc. Head Neck27: 15–21, 2005
Oral Oncology, 1997
This protocol was designed to achieve an improvement in the overall and disease-free survival in locally advanced, previously untreated carcinoma of the head and neck. 53 patients (pts) with locally advanced Stages III and IV, MO squamous cell carcinoma of the nasopharynx, larynx, paranasal sinuses, oral cavity, oropharynx, hypopharynx and one of unknown origin were treated with intensive chemotherapy followed shortly thereafter by radiotherapy. Induction chemotherapy consisted of two cycles of cisplatin 100 mg/m' over 60 min on day 1, plus 5FU 1000 mg/m' continuous infusion over 24 h on days 2-5, with a lo-day interval between the two cycles, followed by definitive radiotherapy after 10 days. The overall response rate to chemotherapy was 79%, with a 28% complete response (CR) rate and a 51% partial response (PR) rate. The overall CR rate after radiotherapy was 70%. With a median follow-up period of 48 months, the 5-year actuarial survival and disease-free survival rates were 67% and 45%, respectively. No difference was found in the survival probability of pts with carcinoma of the nasopharynx, larynx or other primary sites. The survival of pts with a performance status (PS) (1 was better than pts with PS>l, 72% versus 51% (not significant). The survival probability of complete responders to chemotherapy was superior than the survival of non-complete responders to chemotherapy, 100% versus 54% [P = O.OOl]. The main toxicity was mucositis during radiotherapy. In conclusion, this treatment regimen demonstrated a high CR rate and survival probability in pts with locally advanced and mostly inoperable head and neck cancer.
Acta Oto-Laryngologica, 2008
Both concurrent and sequential chemoradiotherapy have been reported to be good alternatives to total laryngectomy in patients with locally advanced hypopharyngeal cancer. We retrospectively reviewed the results of concurrent vs sequential chemoradiotherapy in two institutions for treatment of locally advanced resectable hypopharyngeal cancer in an effort to optimize future laryngeal preservation treatment. Methods: Seventy-two patients with locally advanced resectable hypopharyngeal squamous cell carcinoma were reviewed. Arm I included 38 patients treated by concurrent chemoradiotherapy (CCRT) while arm II included 34 patients received sequential chemoradiotherapy. In arm I patients received CCRT of cisplatin 100 mg/m 2 d1, 22 of radiotherapy at dose of 65 Gy/1.8-2 Gy/f, 5 days/week. Patients in arm II received 2 cycles of induction chemotherapy consisted of 5-fluorouracil 1000 mg/m 2 on d1-4 on 24 h continuous infusion plus cisplatin 100 mg/m 2 d1; cycle was repeated every 3 weeks followed by radiotherapy as in arm I. Results: Demographic data were balanced in both arms. The median age was 50 and 48 years in arm I and II respectively. There was male predominance in both arms. Most of the patients were of ECOGPS of 1and of stage III. No recorded deaths due to treatment toxicities .But as expected CCRT was associated with higher toxicity. In order of frequency; mucositis, anemia were higher in arm I. Significantly higher response rate was observed in arm I (p = 0.04).Three-year survival rates were 74% in arm I and 67.9% in arm II with no significant difference (p = 0.074) but 3-year PFS rate was significantly higher in arm I (52.6% vs. 47%) (p = 0.03). Laryngeal-preservation rate was 78% in arm I vs. 56% in arm II with significant difference. Conclusion: There was higher benefit of concurrent chemo-radiotherapy over sequential chemoradiotherapy. However, larger number of patients and prospective randomized trials are needed to confirm our findings. New strategies that improve organ preservation with less toxicity are needed.
Update in the management of head and neck cancer
Update on Cancer Therapeutics, 2006
Patients with head and neck cancer present numerous challenges to treating physicians. The optimum management requires a coordinated , multispeciality team, comprising experienced head and neck surgeons, medical and radiation oncologists, pathologists, diagnostic radiologists and nuclear medicine physicians. The improved survival observed with CRT using high-dose cisplatin over RT alone warrants its use as standard care for fit patients with high risk SCCHN following surgery or as definitive therapy for patients with unresectable disease. Patients with unresectable disease also have better survival with induction CT and RT compared to RT alone. However, when the goal of therapy is preservation of the larynx, CRT is superior to both induction CT followed by RT, and RT alone. Drugs that inhibit the EGFR pathway, alone or in combination with radiation, appear promising in the treatment of patients with unresectable disease and with recurrent or metastatic disease. Local control rates may improve with wider utilization of altered fractionation schedules in CRT regimens. Intensity modulation and PET-CT fusion are improved means to target and accurately deliver radiation therapy to the head and neck. Endoscopic laser surgery and supracricoid partial laryngectomy can improve organ preservation in suitable patients.
Strahlentherapie Und Onkologie, 2009
Background and Purpose: The optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: Concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m2/d1–5 + 29–33; n = 54) or two courses cisplatin (20 mg/m2/d1–5 + 29–33) + 5-fluorouracil (5-FU; 600 mg/m2/d1–5 + 29–33; n = 74). Results: At least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different. The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week. Conclusion: Two courses of fractionated cisplatin (20 mg/m2/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity. Hintergrund und Ziel: Das optimale Radiochemotherapieregime bei der Behandlung fortgeschrittener Kopf-Hals-Tumoren ist nicht hinreichend geklärt. Diese nichtrandomisierte Studie vergleicht zwei cisplatinbasierte Regimes in einer Serie von 128 Patienten (Tabelle 1) mit lokal fortgeschrittenem (Stadium IV) nichtresektablem Plattenepithelkarzinom der Kopf-Hals-Region (SCCHN). Patienten und Methodik: Die simultan zur Strahlentherapie applizierte Chemotherapie bestand aus zwei Kursen Cisplatin (20 mg/m2/d1–5 + 29–33; n = 54) oder zwei Kursen Cisplatin (20 mg/m2/d1–5 + 29–33) + 5-Fluorouracil (5-FU; 600 mg/m2/ d1–5 + 29–33; n = 74). Ergebnisse: Mindestens eine Grad-3-Toxizitat trat bei 25 von 54 Patienten (46%) unter alleiniger Cisplatingabe und bei 52 von 74 Patienten (70%) unter Cisplatin + 5-FU auf. Das letztgenannte Regime war insbesondere mit hoheren Raten an Mukositis (p = 0,027) und akuter Hauttoxizitat (p = 0,001) assoziiert (Abbildung 1). Sieben von 54 (13%) und 20 von 74 Patienten (27%) erhielten toxizitatsbedingt nur einen Kurs Chemotherapie. Die Spattoxizitat (Xerostomie, Halsfibrose, Hauttoxizitat, Lymphodem) war in beiden Gruppen vergleichbar (Abbildung 2). Die Raten fur die lokoregionale Kontrolle nach 2 Jahren betrugen 67% nach alleiniger Cisplatingabe sowie 52% nach Cisplatin + 5-FU (p = 0,35; Abbildung 3). Die Raten fur das metastasenfreie Uberleben lagen bei 79% und 69% (p = 0,65; Abbildung 4), die Raten für das Gesamtüberleben bei 70% und 51% (p = 0,10; Abbildung 5). In der Multivarianzanalyse waren die Therapieergebnisse signifikant mit dem Allgemeinzustand, der T-Kategorie, der N-Kategorie, dem Hamoglobinwert vor Strahlentherapie und einer Radiotherapiepause > 1 Woche assoziiert (Abbildung 3, Tabelle 2). Schlussfolgerung: Das aus alleiniger fraktionierter Cisplatingabe (20 mg/m2/d) bestehende Regime scheint besser geeignet zu sein als die Kombination Cisplatin + 5-FU. Das erstgenannte Regime führte zu vergleichbaren Therapieergebnissen, war allerdings mit signifikant geringerer Akuttoxizitat assoziiert als die Kombination Cisplatin + 5-FU.
Japanese Journal of Clinical Oncology
Background: Induction chemotherapy for patients with head and neck cancer is widely performed, and several advantages of induction chemotherapy have been reported. However, there is currently insufficient evidence to strongly recommend induction chemotherapy. In this study, we analyzed the outcomes for patients treated with induction chemotherapy and subsequent definitive treatments. Methods: Operable patients with untreated oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinoma treated with induction chemotherapy were included in this retrospective study. We conducted induction chemotherapy using docetaxel, cisplatin and 5-fluorouracil and performed subsequent surgical treatment or radiotherapy according to the response to induction chemotherapy. Results: A total of 65 patients were included in this study, and 50 patients (76.9%) had Stage IV tumors. The response to induction chemotherapy was CR in two patients, PR in 55 patients, and SD in eight patients. The subsequent definitive treatment was radiotherapy in 60 patients, and surgery in five patients. The 3-year overall survival rates for patients who received radiotherapy and surgery were 88.4% and 75.0%, respectively (P = 0.30). The 3-year disease-free survival rates for patients who received radiotherapy and surgery were 68.0% and 0%, respectively (P = 0.01). The 3-year laryngeal dysfunction free survival rates for patients who received RT and surgery were 77.8% and 0%, respectively (P < 0.01). Conclusions: We achieved favorable survival outcomes and high larynx preservation rates. Our results suggest that induction chemotherapy using TPF regimen is one of the optimal treatment strategies when treating head and neck cancers. Further prospective studies with a larger cohort are required to confirm our findings.