Chemoradiation therapy

A multicenter, randomized, controlled, phase III trial (NCT01872962) compared gemcitabine and cisplatin induction chemotherapy plus concurrent chemoradiation therapy with concurrent chemoradiation therapy alone. At a median follow-up of 42.7 months, the 3-year recurrence-free survival rate was 85.3% for patients in the induction chemotherapy group and 76.5% for patients in the standard therapy group (stratified hazard ratio [HR] recurrence or death, 0.51; 95% CI, 0.34–0.77; P = .001).[30][Level of evidence B1] In a multicenter phase III trial, patients were randomly assigned to receive either concurrent chemoradiation therapy alone (standard therapy, n = 238) or gemcitabine and cisplatin induction chemotherapy before concurrent chemoradiation therapy (n = 242). With a median follow-up of 69.8 months, patients in the induction chemotherapy group had a significantly higher 5-year OS rate (87.9%) than those in the standard therapy group (78.8%) (HR, 0.51; 95% CI, 0.34–0.78; P = .001). The risk of late toxicities was comparable (grade 3 or higher toxicity, 11.3% vs. 11.4%).[32][Level of evidence B1]

Chemoradiation therapy followed by adjuvant chemotherapy was used in the INT-0099 trial.[16][Level of evidence C1]

Chemoradiation therapy followed by adjuvant chemotherapy was used in the INT-0099 trial.[16][Level of evidence C1]

Patients with parapharyngeal extension were originally staged as T3 in the INT-0099 study and are now considered T2 in the current staging.

Chemoradiation therapy followed by adjuvant chemotherapy was used in the INT-0099 trial.[16][Level of evidence C1]

The control rate at 3 years was 91.7% in the radiation therapy group (median follow-up period, 34 months) and 100% in the chemoradiation and adjuvant chemotherapy group (median follow-up period, 44 months) (P =.10). The 3-year disease-free survival (DFS) rate was 91.7% in the radiation therapy group and 96.9% in the chemoradiation and adjuvant chemotherapy group (P =.66).

Three randomized prospective trials compared combination chemotherapy (i.e., cisplatin, epirubicin, and bleomycin or cisplatin plus fluorouracil [5-FU] infusion) plus radiation therapy with radiation therapy alone.[17][Level of evidence A1]; [35,36][Level of evidence B1]

Three randomized prospective trials compared combination chemotherapy (i.e., cisplatin, epirubicin, and bleomycin or cisplatin plus fluorouracil [5-FU] infusion) plus radiation therapy with radiation therapy alone.[17][Level of evidence A1]; [35,36][Level of evidence B1]

Although DFS was improved in the chemotherapy group, for both groups, improvement in OS was reported only from the Intergroup trial in which chemotherapy with cisplatin was given concurrently with radiation therapy.[17]

A study of 1,355 patients compared radiation therapy given concurrently with carboplatin or cisplatin that was administered with a 96-hour infusion of 5-FU monthly for three cycles.[37][Level of evidence A1]

A study of 1,355 patients compared radiation therapy given concurrently with carboplatin or cisplatin that was administered with a 96-hour infusion of 5-FU monthly for three cycles.[37][Level of evidence A1]

The 3-year DFS rate was 63.4% for patients in the cisplatin arm and 60.9% for patients in the carboplatin arm (HR, 0.70; 95% CI, 0.50–0.98; P = .961).

A study of 1,355 patients compared radiation therapy given concurrently with carboplatin or cisplatin that was administered with a 96-hour infusion of 5-FU monthly for three cycles.[37][Level of evidence A1]

OS rates were 77% for patients in the cisplatin arm and 79% for patients in the carboplatin arm (HR, 0.83; 95% CI, 0.63–1.010; P = .988).

A study of 1,355 patients compared radiation therapy given concurrently with carboplatin or cisplatin that was administered with a 96-hour infusion of 5-FU monthly for three cycles.[37][Level of evidence A1]

Toxicity to kidneys and red blood cell count was greater in patients in the cisplatin group.