Phase III Study of Concurrent Chemoradiotherapy Versus
Radiotherapy Alone for Advanced Nasopharyngeal Carcinoma: Positive Effect on Overall and
Progression-Free Survival
Jin-Ching Lin, Jian-Sheng Jan, Chen-Yi Hsu,
Wen-Miin Liang, Rong-San Jiang, Wen-Yi Wang Journal of Clinical Oncology, Vol 21, Issue 4 (February),
2003: 631-637
From the Departments of Radiation Oncology and Otorhinolaryngology,
Taichung Veterans General Hospital; Department of Public Health, China Medical College;
Department of Basic Medicine, Hung Kuang Institute of Technology, Taichung; and Institute
of Clinical Medicine, College of Medicine, National Yang-Ming University, Taipei, Taiwan.
Purpose: Nasopharyngeal carcinoma (NPC) is a radiosensitive and
chemosensitive tumor. This randomized phase III trial compared concurrent
chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in patients with
advanced NPC. From December 1993 to April 1999, 284 patients with
1992 American Joint Committee on Cancer stage III to IV (M0) NPC were randomly
allocated into two arms. Similar dosage and fractionation of RT was
administered in both arms. The investigational arm received two cycles of concurrent chemotherapy with cisplatin 20 mg/m2/d
plus fluorouracil 400 mg/m2/d by 96-hour continuous infusion during
the weeks 1 and 5 of RT. Survival analysis was estimated by the
Kaplan-Meier method and compared by the log-rank test. Baseline
patient characteristics were comparable in both arms. After a median follow-up
of 65 months, 26.2% (37 of 141) and 46.2% (66 of 143) of patients developed
tumor relapse in the CCRT and RT-alone groups, respectively. The 5-year overall survival rates were 72.3% for the CCRT
arm and 54.2% for the RT-only arm (P = .0022). The 5-year
progression-free survival rates were 71.6% for the CCRT group compared with
53.0% for the RT-only group (P = .0012). Although significantly more
toxicity was noted in the CCRT arm, including leukopenia and emesis, compliance
with the combined treatment was good. The second cycle of concurrent
chemotherapy was refused by nine patients and was delayed for 1 week for
another nine patients. There were no treatment-related deaths in either arm.
We conclude that CCRT is superior to RT alone for patients with advanced
NPC in endemic areas.
Nasopharyngeal
Carcinoma Treated With Reduced-Volume Intensity-Modulated Radiation Therapy:
Report on the 3-Year Outcome of a Prospective Series
IJROBP
Purpose
To evaluate the
efficacy of
intensity-modulated radiotherapy (IMRT) using reduced
clinical target volumes (CTV) in the treatment of nasopharyngeal
carcinoma (NPC). Between August 2003 and December 2006, 323 patients
with NPC were treated with IMRT according to this institutional
protocol. Presenting stages were Stage II in 63, Stage III in 166,
and Stage IVA/B in 94 patients. High-risk CTV encompassed gross
tumor volume and entire nasopharyngeal mucosa with a margin. A
reduced CTV was delineated for the remaining subclinical regions
adjacent to the primary disease. Uninvolved neck nodes were
delineated according to the Radiation Therapy Oncology Group (RTOG)
/ European Organisation for Research and Treatment of Cancer (EORTC)
consensus excluding the deep jugular (i.e., lymph nodes in
retrostyloid space above C1 vertebra) and submental nodes. Patients
with locoregionally advanced diseases
also received cisplatin-based
chemotherapy.
Results
With a median
follow-up of 30 months (range, 4–53months), 12, 6, and 26 patients
had developed local, regional, and distant failures, respectively.
The 3-year estimated local
control, regional control, metastasis-free survival, disease-free
survival and overall survival were 95%, 98%, 90%, 85%, and 90%,
respectively. Multivariate analyses revealed that
T-classification had no predictive value for outcome, whereas
N-classification was significant for predicting metastasis-free (p =
0.005) and overall survival (p =0.006). Ten patients (7.8%)
experienced Grade II xerostomia at 24 months after treatment. No
Grade III or IV late-toxicities were observed. Two patients died of
treatment-induced complications.
Concurrent Chemotherapy-Radiotherapy Compared With Radiotherapy Alone in
Locoregionally Advanced Nasopharyngeal Carcinoma: Progression-Free Survival Analysis of a
Phase III Randomized Trial
A.T.C. Chan,
Journal of
Clinical Oncology, Vol 20, Issue 8 (April), 2002: 2038-2044
From the Prince of Wales Hospital, Chinese University of Hong Kong, and
Queen Elizabeth Hospital, Hong Kong.
PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both
radiotherapy (RT) and chemotherapy. This randomized phase III trial compared
concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally
advanced NPC. Patients with Ho’s N2 or N3 stage or N1 stage
with nodal size  4 cm were
randomized to receive cisplatin 40 mg/m2
weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The
primary end point was progression-free survival (PFS). Three hundred
fifty eligible patients were randomized. Baseline patient characteristics were
comparable in both arms. There were significantly more toxicities, including
mucositis, myelosuppression, and weight loss in the CRT arm. There were no
treatment-related deaths in the CRT arm, and one patient died during treatment
in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone
arm (P = .10) with a hazards ratio of 1.367 (95% confidence
interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate
interaction with tumor stage, and a subgroup analysis demonstrated a highly
significant difference in favor of the CRT arm in Ho’s stage T3 (P
= .0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage,
the time to first distant failure was statistically significantly different
in favor of the CRT arm (P = .016). Concurrent CRT is well tolerated in
patients with advanced NPC in endemic areas. Although PFS was not significantly
different between the concurrent CRT arm and the RT-alone arm in the
overall comparison, PFS was significantly prolonged in patients with advanced
tumor and node stages.
Concomitant radiotherapy and chemotherapy for early-stage
nasopharyngeal carcinoma.
Cheng SH, Tsai SY, Y J Clin Oncol; 18(10):2040-5 2000
Early-stage nasopharyngeal carcinoma (NPC) continues to carry a failure rate of 15% to
30% when treated with radiotherapy alone; the benefit of concomitant radiotherapy and
chemotherapy (CCRT) in early-stage NPC is unclear. The purpose of this report is to
describe our efforts to improve treatment outcome in early-stage NPC after CCRT. PATIENTS
AND METHODS: Of 189 newly diagnosed NPC patients without evidence of distant metastases
who were treated in our institution between 1990 and 1997, 44 presented with early-stage
(stage I and II) disease according to the American Joint Committee on Cancer (AJCC) 1997
NPC staging system. Twelve of these patients were treated with radiotherapy alone and 32
with CCRT. Each patient's head and neck area was evaluated by magnetic resonance imaging
or computed tomography. Radiotherapy was administered at 2 Gy per fraction per day, Monday
through Friday, for 35 fractions for a total dose of 70 Gy. Chemotherapy consisting of cis-diamine-dichloroplatinum and fluorouracil
was delivered simultaneously with radiotherapy in weeks 1 and 6 and sequentially for two
monthly cycles after radiotherapy. RESULTS: Patients who were treated with
radiotherapy alone primarily had stage I disease, whereas none of those who were treated
with CCRT had stage I disease (11 of 12 patients v none of 32 patients; P =.001). The locoregional control rate at 3 years for the radiotherapy group was
91.7% (median follow-up period, 34 months) and was 100% for the CCRT group (median
follow-up period, 44 months) (P =.10). The 3-year disease-free survival rate in the
radiotherapy group was 91.7% and was 96.9% in the CCRT group (P =.66).
CONCLUSION: Our results reveal excellent prognosis of AJCC 1997 stage II NPC treated with
CCRT. Stage II patients with a greater tumor burden treated with CCRT showed an equal
disease-free survival, compared with stage I patients treated with radiotherapy alone. A
prospective randomized trial is underway to confirm the role of CCRT in stage II NPC.
J Clin Oncol 1998 Apr;16(4):1310-7
Chemoradiotherapy versus radiotherapy in patients with
advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099.
Al-Sarraf. This randomized phase III trial compared chemoradiotherapy versus
radiotherapy alone in patients with nasopharyngeal cancers. Radiotherapy was administered
in both arms: 1.8- to 2.0-Gy/d fractions Monday to Friday for 35 to 39 fractions for a
total dose of 70 Gy. The investigational arm received chemotherapy with cisplatin 100
mg/m2 on days 1, 22, and 43 during radiotherapy; postradiotherapy, chemotherapy with
cisplatin 80 mg/m2 on day 1 and fluorouracil 1,000 mg/m2/d on days 1 to 4 was administered
every 4 weeks for three courses.The median progression-free survival (PFS) time was 15
months for eligible patients on the radiotherapy arm and was not reached for the
chemo-radiotherapy group. The 3-year PFS rate was 24% versus 69%, respectively (P <
.001). The median survival time was 34 months for the radiotherapy group and not reached
for the chemo-radiotherapy group, and the 3-year survival rate was
47% versus 78%, respectively (P = .005). One hundred eighty-five patients were
included in a secondary analysis for survival. The 3-year survival rate for patients
randomized to radiotherapy was 46%, and for the chemoradiotherapy group was 76% (P <
.001).
Int J Radiat Oncol Biol Phys 1995 Oct 15;33(3):569-77
A prospective randomized study of chemotherapy adjunctive
to definitive radiotherapy in advanced nasopharyngeal carcinoma.
Chan. Eighty-two patients with histologically proven nasopharyngeal carcinoma who had
either Ho's N3 staging or any N stage with a nodal diameter of > or = 4 cm were
entered. Seventy-seven patients were evaluated for tumor response and survival. The
patients were randomized to receive two cycles of cisplatin 100 mg/m2 Day 1,5-fluorouracil
1000 mg/m2 24-h infusion Days 2, 3, and 4 before radical radiotherapy, and four cycles of
postradiotherapy chemotherapy (37 patients) or radiotherapy alone (40 patients). All
patients received radical radiotherapy to the nasopharynx and neck. The nasopharynx and
upper neck were treated to 66 Gy by conventional fractionation and the lower neck to 58
Gy. Booster radiotherapy (7.5 Gy/two fractions/week) was given to any residual nodes after
standard radiotherapy.The overall complete response rate to chemoradiotherapy was 100%,
and to radiotherapy alone, 95%. The 2-year overall survival was 80%
in the chemoradiotherapy arm and 80.5% in the radiotherapy arm. The 2-year
disease-free survival was 68% in the chemoradiotherapy arm and 72% in the radiotherapy
arm, without significant difference between the two arms.
Int J Radiat Oncol Biol Phys 1992;23(2):261-270
Retrospective analysis of 5037 patients with
nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of
failure.
Lee. An analysis of 5037 patients with squamous cell carcinoma of the nasopharynx
treated during the years 1976-1985. The stage distribution according to Ho's
classification was 9% Stage I, 13% II, 50% III, 22% IV, and 6% Stage V. Only 4488 (89%)
patients had a full course of megavoltage radiation therapy. The median equivalent dose to
the nasopharyngeal region was 65 Gy and cervical region in node-positive
patients 53 Gy. The overall actuarial 10-year survival rate was 43%,
and the corresponding failure-free survival 34%.
Int J Radiat Oncol Biol Phys 1997 Mar 15;37(5):985-996
Carcinoma of the nasopharynx treated by radiotherapy
alone: determinants of local and regional control.
Sanguineti The results of treatment and to identify prognostic factors for local and
regional control in a population of 378 patients with nasopharyngeal
carcinomas treated in a single institution by radiation therapy alone. There were 286
males and 92 females with a median age of 52 years (range: 16-86 years). The majority of
the patients were Caucasian (282 patients, 75%). Thirty-two patients (8%) had one or more
cranial nerve deficits. Three-fourths of the patients presented with AJCC Stage IV disease
(T4, N0-3, 118 patients; T1-3, N2-3 164 patients). Histologically, 193 tumors (51%) were
squamous cell carcinomas, 154 (41%) lymphoepitheliomas, and 31 (8%) unclassified
carcinomas. Average total dose varied with T-stage and ranged from 60.2 to 72.0 Gy. Median
follow-up time was 10 years. RESULTS: For the entire population the 5-,
10-, and 20-year actuarial survival rates were 48, 34, and 18%,
respectively, with 184 patients (49%) dying of nasopharyngeal cancer.
Cancer 1976 Jun;37(6):2605-2612
Carcinoma of the nasopharynx. Eighteen years' experience
with megavoltage radiation therapy.
Hoppe. 82 patients with carcinoma of the nasopharynx received high dose megavoltage
radiation therapy at Stanford University. The actuarial disease-free (NED)
survival was 62% at 5 years and 56% at 10 years. The NED survivals at
5 years for patients with T1, T2, and T3 lesions were 76%, 68%, and
55%, respectively. No T4 patients were salvaged
Laryngoscope 1992 Sep;102(9):965-972
Nasopharyngeal carcinoma: treatment results with primary
radiation therapy.
Bailet . One hundred three patients with nasopharyngeal carcinoma were treated with
radiotherapy at UCLA Medical Center from January 1955 to December 1990.. Overall 5- and 10-year actuarial survival rates for all patients were 58%
and 47%, respectively. Disease-free survival rates at 3 and 5 years were 45% and
30%, respectively. |
