A Phase II study of docetaxel and carboplatin as neoadjuvant therapy for nasopharyngeal carcinoma with early T status and advanced N status.
BACKGROUND
Promising results from a Phase II trial of induction chemotherapy and sequential radiotherapy for advanced nasopharyngeal carcinoma (NPC) at The University of Texas M. D. Anderson Cancer Center (Houston, TX) and two retrospective reviews of the authors' historical experience with NPC demonstrated that distant failure was directly correlated with advanced lymph node status. Furthermore, local control was excellent for patients with T1-3 disease that was managed with radiation alone or with a sequential approach involving chemotherapy. Neoadjuvant chemotherapy (primarily with cisplatin + 5-fluorouracil) was associated with a significantly decreased risk of distant metastasis and with improved survival. Based on these findings, the authors evaluated a novel induction regimen involving docetaxel and carboplatin for patients with previously untreated T1-2N2-3M0 NPC.


METHODS
Docetaxel (80 mg/m2 on Day 1) and carboplatin (to an area under the time-concentration curve of 6 on Day 1) were administered every 21 days for 3 cycles, after which radiotherapy was administered. NPC was restaged with magnetic resonance imaging and nasopharyngoscopy 3 weeks after the completion of chemotherapy and 6 weeks after the completion of radiotherapy.


RESULTS
Over 5 years, 18 patients were enrolled in the study. Grade 4 neutropenia and Grade 2 fatigue were observed in 51% and 28% of chemotherapy courses, respectively. After chemotherapy, 2 patients had complete responses, 14 had partial responses, 1 had a minor response, and 1 had progressive disease. The latter two patients and one patient who had a partial response underwent off-study chemoradiotherapy. After radiotherapy or chemoradiotherapy, 12 patients had complete responses and 6 had partial responses. Seven patients had recurrent disease; two had local recurrences, and five had distant metastases.


CONCLUSIONS
Although unlikely to be superior to cisplatin + 5-fluorouracil, the trial regimen could be administered quickly in the outpatient setting, was logistically more convenient for the patient, and was devoid of serious nonhematologic toxic effects. We believe that the risk-based approach examined in the current study merits further investigation.
Johnson
Faye M
FM
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Garden
Adam
A
Palmer
J Lynn
JL
Kies
Merrill
M
Clayman
Gary
G
Brumfield
Brenda
B
Khuri
Fadlo R
FR
Morrison
William
W
Papadimitrakopoulou
Vassiliki
V
Diaz
Eduardo M
EM
Glisson
Bonnie S
BS
D000328:Adult; D000368:Aged; D016190:Carboplatin / Q000008:administration & dosage*; D002277:Carcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D018570:Risk Assessment; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage*; D016896:Treatment Outcome
D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin