Toxicity induced by radiochemotherapy with weekly paclitaxel versus weekly cisplatin in patients with advanced head and neck cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16534-16534
Author(s):  
D. L. Stanculeanu ◽  
A. Tache ◽  
A. Cringeanu ◽  
D. Mitulescu ◽  
R. Scheusan ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Side Effects ◽  
Head And Neck ◽  
Neck Cancer ◽  
Locally Advanced ◽  
External Beam Radiation ◽  
Weekly Paclitaxel ◽  
Severe Side Effect ◽  
Advanced Head ◽  
Grade 3

16534 Background: Head and neck cancers represent about 8 % of the total solid cancer cases. For advanced head and neck cancer (HNC) patients, the effects of disease and the side effects of aggressive treatments have the potential to severely affect quality of life. Combined chemoradiotherapy increase rates of locoregional control, but it may cause severe side effects, mainly painful mucositis. In our study we evaluated the chemoradiotherapy induced toxicities in patients treated with concomitant radiochemotherapy using weekly paclitaxel or cisplatin for advanced head and neck cancer. Methods: From April 2003 to December 2005 46 patients with locally advanced head and neck cancer were enrolled onto this study. Patients characteristics: 35 male and 11 female; mean age 62,5; performance status ECOG 0–1, carcinoma histological confirmed. All patients received external beam radiation using DT= 45 Gy, 1,8 Gy/fr, 5 fr/week in combination with chemotherapy: arm A (20 pts) - Paclitaxel 35 mg/mp days 1,8,15,22,29; arm B (26 pts)- Cisplatin 20 mg/mp days 1,8,15,22,29. Results: 40 patients have completed the planed treatment; 4 patients have interrupted treatment because of toxicity; there were 2 toxic death due to neutropenic sepsis and metabolic disorders in arm A. Toxicity grade 3–4 was hematological - neutropenia - 14, 6 % pts in arm A vs. 7, 8 % pts in arm B; gastrointestinal - nausea 6,7 % pts in arm A vs. 5,6% pts in arm B; neurological - neuropathy 5,4 % pts in arm A vs. 0 pts in arm B; dermatological - radic dermitis 4,3% in arm A vs. 4,1% in arm B; oral mucositis 33,6% in arm A vs 27,8% in arm B. All this patients received analgesics and anti-inflammatory drugs, systemic and/or topical. Other toxicities were not significantly related. Conclusions: This study confirmed that radiochemotherapy has shown to provide clinical benefit response and disease stabilization in patients with locally advanced head and neck cancer. Unfortunately, this concomitant therapy was significantly associated with hematological toxicities and oral mycosis. The most severe side effect was oral mycositis grade 3–4, especially in the paclitaxel arm. No significant financial relationships to disclose.

Compliance and Outcomes in Locally Advanced Head and Neck Cancer Patients Treated with Alternating Chemoradiotherapy in Clinical Practice

2003 ◽  
Vol 89 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Vittorio Franciosi ◽  
Marco Fumagalli ◽  
Luciana Biscari ◽  
Roberto Martinelli ◽  
Teore Ferri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Head And Neck Cancer ◽  
Clinical Practice ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Locally Advanced ◽  
Hematologic Toxicity ◽  
Advanced Head ◽  
Grade 3

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.

Compliance, toxicity and efficacy in weekly versus 3-weekly cisplatin concurrent chemoradiation in locally advanced head and neck cancer

2018 ◽  
Vol 18 (1) ◽  
pp. 21-25 ◽  
Author(s):  
Sandeep Muzumder ◽  
Nirmala Srikantia ◽  
Ganesha Dev Vashishta ◽  
Avinash H. Udayashankar ◽  
John Michael Raj ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Concurrent Chemoradiation ◽  
Advanced Head ◽  
Flat Dose ◽  
Grade 3 ◽  
Weekly Cisplatin

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.

scholarly journals Genetic Variants as Predictive Markers for Ototoxicity and Nephrotoxicity in Patients with Locally Advanced Head and Neck Cancer Treated with Cisplatin-Containing Chemoradiotherapy (The PRONE Study)

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 551 ◽  
Author(s):  
Chantal M. Driessen ◽  
Janneke C. Ham ◽  
Maroeska te Loo ◽  
Esther van Meerten ◽  
Maurits van Lamoen ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Side Effects ◽  
Creatinine Clearance ◽  
Head And Neck ◽  
Neck Cancer ◽  
Genetic Variants ◽  
Locally Advanced ◽  
Added Value ◽  
Advanced Head ◽  
Patient Reported

Ototoxicity and nephrotoxicity are potentially irreversible side effects of chemoradiotherapy with cisplatin in locally advanced head and neck cancer (LAHNC) patients. Several predictive genetic variants have been described, but as yet none in LAHNC patients. The aim of this study is to investigate genetic variants as predictors for ototoxicity and nephrotoxicity in LAHNC patients treated with cisplatin-containing chemoradiotherapy. Our prospective cohort of 92 patients was genotyped for 10 genetic variants and evaluated for their association with cisplatin-induced ototoxicity (ACYP2, COMT, TPMT and WFS1) and nephrotoxicity (OCT2, MATE and XPD). Ototoxicity was determined by patient-reported complaints as well as tone audiometrical assessments. Nephrotoxicity was defined as a decrease of ≥25% in creatinine clearance during treatment compared to baseline. A significant association was observed between carriership of the A allele for rs1872328 in the ACYP2 gene and cisplatin-induced clinically determined ototoxicity (p = 0.019), and not for ototoxicity measured by tone audiometrical assessments (p = 0.449). Carriership of a T allele for rs316019 in the OCT2 gene was significantly associated with nephrotoxicity at any time during chemoradiotherapy (p = 0.022), but not with nephrotoxicity at the end of the chemoradiotherapy. In conclusion, we showed prospectively that in LAHNC patients genetic variants in ACYP2 are significantly associated with clinically determined ototoxicity. Validation studies are necessary to prove the added value for individualized treatments plans in these patients.

A phase I/II trial of induction chemotherapy followed by concomitant docetaxel with concomitant boost radiotherapy (CBR) and amifostine for advanced head and neck cancer (HNC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15525-15525 ◽  
Author(s):  
C. Saurel ◽  
R. Meredith ◽  
J. A. Bonner ◽  
G. Peters ◽  
W. Carroll ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Side Effects ◽  
Phase I ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Neck Cancer ◽  
Distant Metastasis ◽  
Locally Advanced ◽  
Primary Chemotherapy ◽  
Advanced Head

15525 Background: Concomitant chemo-radiation for head and neck cancer has emerged as the optimal method of treating advanced head and neck cancers, although the acute and late toxicities can be formidable. The addition of induction chemotherapy to concomitant chemo-radiation for head and neck cancer is designed to impact the incidence of distant metastasis while delivering aggressive local treatment. This trial evaluates the tolerability and effectiveness of induction chemotherapy followed by CBR with concurrent docetaxel and subcutaneous (SC) amifostine in locally advanced squamous cell carcinoma of the head and neck (SCCHN). Methods: Patients with stage III/IV nonmetastatic SCCHN received 3 cycles of primary chemotherapy with docetaxel and cisplatin, each at 75 mg/m2. Patients then received 4 weekly doses of docetaxel at 20 mg/m2 with concurrent CBR. SC amifostine was given at a dose of 500 mg in divided doses during each day of XRT. Results: The phase I component defined the MTD of concurrent docetaxel as 20 mg/m2 for 4 cycles during CBR. 18 patients are evaluated for response. No patient developed progressive disease during primary chemotherapy. Grade 3–4 mucositis was common, but all patients completed the planned concomitant docetaxel. At 6 months after treatment, 7/18 patients still used a feeding tube, though most have had them subsequently removed. Amifostine given by SC was well tolerated; 7 patients developed transient hypotension not requiring any intervention, with grade1 dermatitis and nausea reported. 2 patients discontinued amifostine due to rash or persistent hypotension. Conclusions: Response to induction chemotherapy was greater then 75% by radiological assessment, with no patient developing distant metastasis thus far. Local control has been excellent but side effects from docetaxel and CBR have necessitated prolonged use of feeding tubes for up to 6 months. SC amifostine has been well tolerated without significant side effects. This aggressive therapy is effective treatment for locally advanced SCCHN. No significant financial relationships to disclose.

Phase II trial of cisplatin, fluorouracil, and pure folinic acid for locally advanced head and neck cancer: a pharmacokinetic and clinical survey.

1995 ◽  
Vol 13 (7) ◽  
pp. 1656-1662 ◽  
Author(s):  
M Schneider ◽  
M C Etienne ◽  
G Milano ◽  
A Thyss ◽  
J Otto ◽  
...  
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Folinic Acid ◽  
Neck Cancer ◽  
Locally Advanced ◽  
Plasma Concentrations ◽  
Response Rates ◽  
Advanced Head ◽  
Primary Tumor Site ◽  
Grade 3

PURPOSE To analyze clinical and pharmacokinetic data of cisplatin (CP)/fluorouracil (FU)/l folinic acid (l FA) chemotherapy administered as first-line treatment to locally advanced head and neck cancer patients. PATIENTS AND METHODS Thirty-nine patients (35 men and four women; median age, 60 years; six stage III and 33 stage IV) received CP on day 1 (100 mg/m2) followed by l FA (200 mg/m2/d x 5) plus FU (500 mg/m2/d x 5) administered by continuous venous infusion (three cycles planned). Mean plasma concentrations of FU, l FA, and 5-methyltetrahydrofolate (5MTHF) over the cycle were computed. RESULTS Clinical response was assessable for 33 patients. Response rates on the primary tumor site (n = 33) were 63.7% complete responses (CRs), 24.2% partial responses (PRs), and 12.1% treatment failures. Response rates on lymph nodes (n = 27) were 40.7% CRs, 37.1% PRs, and 22.2% treatment failures. The most frequent toxicity was mucositis (36.2% of cycles grade 3 to 4). Grade 3 to 4 nausea-vomiting, diarrhea, neutropenia, and thrombocytopenia occurred in 6.7%, 1.9%, 13.3%, and 1% of cycles, respectively. Pharmacokinetic analysis showed a wide interpatient variability for both FU (mean, 1.01 mumol/L; range, 0.16 to 2.09), l FA (mean, 1.89, mumol/L; range, 0.52 to 7.88) and 5MTHF plasma concentrations (mean, 3.85 mumol/L; range, 1.30 to 8.11). A significant correlation was demonstrated between FU concentration and hematologic toxicity grade, mucositis grade, and nausea-vomiting/diarrhea grade. Regarding tumor response, patients who failed to respond significantly exhibited lower FU and total folate concentrations than patients with a CR or PR. CONCLUSION This study highlights the efficacy of CP/FU/l FA in head and neck carcinoma and establishes the clinical importance of coupled FU/FA pharmacokinetics to predict pharmacodynamic variability.

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