Phase II Study with Docetaxel and Cisplatin in the Treatment of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck

Abstract

Purpose: Since the combination of cisplatin and docetaxel have demonstrated activity in squamous cell carcinomas of the lung and oesophagus before, promising results in recurrent metastatic head and neck cancer were expected. Patients and Methods: Between September 1998 and October 2000, 40 patients entered this trial, 38 of whom were evaluable. Six patients were previously untreated, 24 had surgery and/or radiotherapy and 13 had received chemoradiation and/or surgery. Therapy consisted of 75 mg/m² docetaxel (1-hour infusion) and 75 mg/m² cisplatin (90-min infusion) on day 1, repeated every three weeks for a maximum of 6 courses. All patients received corticosteroids routinely, 5-HT3-antagonists, and hydration. Results: The overall response rate was 52.5% (95% confidence interval, 36.1 to 68.5%) including 7 complete (17.5% complete response; CR) and 14 partial remissions (35% partial response; PR). The overall response rate in patients who had no prior treatment (n = 6) was 100%, including 3 CR and 3 PR. In patients who had prior surgery and/or radiotherapy (n = 21) an overall response rate of 42.8% was observed, including 2 CR and 7 PR; 8 patients (38.1%) had stable disease, while disease progressed in 3 (14.3%). Six of 13 patients (46.2%) who had prior chemoradiation ± surgery responded, including 2 CR (15.4%) and 4 PR (30.8%), no change was seen in 4 patients (30.8%) and tumour progressed in 2 (15.4%). The median response duration for all patients was 10 months (range, 3–20), the median overall survival was 11 months (range, 1–30). Myelosuppression was commonly observed; WHO grade 3 or 4 neutropenia occurred in 12 patients (30%) each, and was complicated by septicaemia in 5 cases. WHO grade 3 anaemia was observed in only 3 patients (7.5%). Severe non-hematologic toxicity except for alopecia was rarely observed, and included diarrhea in 2 (5%), nausea/vomiting in 2 patients (5%) and stomatitis in 1 patient (2.5%). Conclusion: Our data suggest that docetaxel and cisplatin in combination is an effective and fairly well tolerated regimen for the treatment of head and neck cancer with an excellent response rate in previously untreated patients.

RASSF1A and ERCC1 Expression Levels Might Be Predictive of Prognosis in Advanced, Recurrent, and Metastatic Squamous Cell Carcinoma of the Head and Neck Treated with Docetaxel and Cisplatin

“…In this retrospective analysis of cisplatin/docetaxel chemotherapyatreduceddosesinpatientswithadvanced,recurrent, ormetastaticSCCHN,theoverallobjectiveresponseratewas 35%,including12%completeremissionand23%partialre- [16][17][18][19]33].Inthesetrials,docetaxelwasadministeredatdosagesrangingfrom75to100mg/m 2 ,andcisplatinwasadministered at dosages ranging from 70 to 75 mg/m 2 on a 3-week schedule.Thereportedresponseratesrangedfrom27to53%, andthemediansurvivalrangedfrom5to12months.Inthe present study, the response rate was 35%, comparable with those in the previous studies. However, compared with the previous results, a fairly long OS was observed in this study population,althoughallpatientseventuallyprogressed.This resultmaybepartiallyexplainedbyrecentadvancesinradiation technology, supportive care, and/or chemotherapeutic agents.Currently,morepatientscanreceiverescuetreatment of re-irradiation or second-line chemotherapy.…”

“…Moreaccurateandobjectivequantitation,suchasreal-time reversetranscriptionpolymerasechainreactionandcorrelationwithIHC,shouldbewarranted.ForRASSF1A,aquanDespite the reduced dose intensity used in the current study, the toxicity profile was similar to those of previous trials. In earlier studies using higher dose intensities, grades 3/4neutropeniawasobservedinupto75%ofpatients [17], andtreatment-relatedmortalitywasobservedinupto16%of patients [33].Treatmentdelayanddosereductionduetotoxicity were reported in up to 42.5% [18] and 24% of patients [17],respectively.Becauseofthesetoxicities,thecombination regimen is not considered feasible in patients with a performance status of 2 [33]. In the present study using 60 mg of docetaxel and 65 mg/m 2 of cisplatin, half of the patients stillshowedgrade3or4neutropenia,andtreatment-related mortalitieswereobservedin11%ofpatients.Moreover,27% of the total chemotherapy was performed at reduced doses, duetotoxicities.Therefore,itisdesirablethatthecombination of docetaxel and cisplatin chemotherapy treatments shouldbeconsideredonlyinpatientsselectedbyusingareliablebiomarker.…”

“…Due to its significant activity as a single agent in patients with advanced or recurrent/metastatic SCCHN, docetaxel is frequentlyusedincombinationwithcisplatin [12][13][14][15].When the drug is combined with cisplatin, the response rate has beenreportedtorangefrom27to53%,andthemedianoverall survival (OS) has ranged from 5 to 12 months [16][17][18][19][20]. However, the improved efficacy achieved with combination therapy did not translate into survival advantage compared to that of single-agent treatment in a variety of randomized trials.…”

Paclitaxel, cisplatin and 5-fluorouracil in recurrent squamous cell carcinoma of the head and neck: A phase II trial from an Italian cooperative group

“…In relapsed disease phase II studies of docetaxel in combination with cisplatin gave response rates similar to those achievable with cisplatin and 5-fluorouracil [23,24] but data of comparison of the two regimens from a randomized trial are not yet available. Moreover, data on the triplet including cisplatin, docetaxel and 5-fluorouracil are lacking.…”

The challenging integration of platinum compounds, taxanes, and molecular-targeted therapies in the multidisciplinary treatment of squamous cell carcinoma of the head and neck

“…Docetaxel administered every 3 weeks is probably more active and associated with more hematological adverse events than when administered on a weekly schedule, while weekly paclitaxel may be better tolerated and more efficacious than when given every 3 weeks. Because of this important activity, combinations of paclitaxel/cisplatin, paclitaxel/carboplatin and docetaxel/cisplatin have been experienced in patients with good performance status [20][21][22]. Later 5-fluorouracil was added to these combinations in the recurrent disease as well as induction chemotherapy with promising results as mentioned earlier.…”