Concurrent Chemoradiation Therapy

A meta-analysis that originally included 93 randomized prospective head and neck cancer trials published between 1965 and 2000 was updated with the addition of 16 new trials (including 2,767 patients) and 11 updated trials. The results confirmed the benefit and superiority of the addition of concurrent chemotherapy for nonmetastatic head and neck cancer.[31,32][Level of evidence A2]

A meta-analysis that originally included 93 randomized prospective head and neck cancer trials published between 1965 and 2000 was updated with the addition of 16 new trials (including 2,767 patients) and 11 updated trials. The results confirmed the benefit and superiority of the addition of concurrent chemotherapy for nonmetastatic head and neck cancer.[31,32][Level of evidence A2]

The subset of patients who received chemotherapy and radiation therapy had a 6.5% absolute survival advantage, with OS increasing from 27.7% to 33.6% at 5 years and from 17.3% to 20.9% at 10 years.

A meta-analysis that originally included 93 randomized prospective head and neck cancer trials published between 1965 and 2000 was updated with the addition of 16 new trials (including 2,767 patients) and 11 updated trials. The results confirmed the benefit and superiority of the addition of concurrent chemotherapy for nonmetastatic head and neck cancer.[31,32][Level of evidence A2]

Patients who received concurrent chemotherapy had a greater survival benefit than did those who received neoadjuvant chemotherapy.

Postoperative chemoradiation therapy with cisplatin 100 mg/m2 given once every 3 weeks is standard treatment for patients with disease at high risk for recurrence, mainly those with extracapsular lymph node extension and positive surgical margins. However, this dosage has raised concerns about insufficient cisplatin delivery because of high-dose–related toxicity. Chemoradiation therapy with weekly cisplatin is widely used as an alternative with a better safety profile. A multi-institutional, open-label, noninferiority, phase II/III trial compared different cisplatin schedules as part of postoperative treatment for patients with high-risk locally advanced SCC of the head and neck. Patients received either cisplatin (40 mg/m2) once weekly or standard-dose cisplatin (100 mg/m2) once every 3 weeks, both combined with radiation therapy. OS was the primary end point of the phase III portion of the study. An HR of 1.32 was set as the noninferiority margin. A total of 261 patients were enrolled (cisplatin every 3 weeks, 132 patients; cisplatin weekly, 129 patients).[33] Regimens with cisplatin given weekly or every 3 weeks are both considered standard care. A large, randomized, prospective trial is evaluating the equivalent efficacy of these regimens.

Postoperative chemoradiation therapy with cisplatin 100 mg/m2 given once every 3 weeks is standard treatment for patients with disease at high risk for recurrence, mainly those with extracapsular lymph node extension and positive surgical margins. However, this dosage has raised concerns about insufficient cisplatin delivery because of high-dose–related toxicity. Chemoradiation therapy with weekly cisplatin is widely used as an alternative with a better safety profile. A multi-institutional, open-label, noninferiority, phase II/III trial compared different cisplatin schedules as part of postoperative treatment for patients with high-risk locally advanced SCC of the head and neck. Patients received either cisplatin (40 mg/m2) once weekly or standard-dose cisplatin (100 mg/m2) once every 3 weeks, both combined with radiation therapy. OS was the primary end point of the phase III portion of the study. An HR of 1.32 was set as the noninferiority margin. A total of 261 patients were enrolled (cisplatin every 3 weeks, 132 patients; cisplatin weekly, 129 patients).[33] Regimens with cisplatin given weekly or every 3 weeks are both considered standard care. A large, randomized, prospective trial is evaluating the equivalent efficacy of these regimens.

At the planned third interim analysis in the phase III part of the trial, after a median follow-up of 2.2 years, chemoradiation therapy with weekly cisplatin was noninferior to cisplatin every 3 weeks in terms of OS (HR, 0.69; 99.1% CI, 0.374–1.273 [<1.32]; one-sided P for noninferiority = .0027).[33][Level of evidence A1]

Postoperative chemoradiation therapy with cisplatin 100 mg/m2 given once every 3 weeks is standard treatment for patients with disease at high risk for recurrence, mainly those with extracapsular lymph node extension and positive surgical margins. However, this dosage has raised concerns about insufficient cisplatin delivery because of high-dose–related toxicity. Chemoradiation therapy with weekly cisplatin is widely used as an alternative with a better safety profile. A multi-institutional, open-label, noninferiority, phase II/III trial compared different cisplatin schedules as part of postoperative treatment for patients with high-risk locally advanced SCC of the head and neck. Patients received either cisplatin (40 mg/m2) once weekly or standard-dose cisplatin (100 mg/m2) once every 3 weeks, both combined with radiation therapy. OS was the primary end point of the phase III portion of the study. An HR of 1.32 was set as the noninferiority margin. A total of 261 patients were enrolled (cisplatin every 3 weeks, 132 patients; cisplatin weekly, 129 patients).[33] Regimens with cisplatin given weekly or every 3 weeks are both considered standard care. A large, randomized, prospective trial is evaluating the equivalent efficacy of these regimens.

Grade 3 or 4 neutropenia and infection were less frequent in patients who received cisplatin weekly. Grade 3 or 4 neutropenia occurred in 49% of patients who received cisplatin every 3 weeks and 35% of patients who received cisplatin weekly. Grade 3 or 4 infection occurred in 12% of patients who received cisplatin every 3 weeks and 7% of patients who received cisplatin weekly. Grade 3 or 4 renal impairment and hearing impairment were also less frequent in patients who received cisplatin weekly. No treatment-related deaths were reported among patients who received cisplatin every 3 weeks, and two deaths were reported among patients who received weekly cisplatin (1.6%).

A phase III randomized trial in India included patients with locally advanced SCC of the head and neck unsuitable for cisplatin-based chemoradiation. This study evaluated using docetaxel as a radiosensitizer. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 were randomly assigned (1:1) to receive either radiation therapy alone or with concurrent docetaxel (15 mg/m2) once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). Most patients (about 60%) received the treatment as definitive. Cisplatin ineligibility was defined by multiple parameters, including an ECOG PS of 2, calculated creatinine clearance <50 mL/min, and organ dysfunction of grade 2 or higher. A total of 356 patients were enrolled (176 in the radiation therapy arm and 180 in the radiation-and-docetaxel arm).[34]

A phase III randomized trial in India included patients with locally advanced SCC of the head and neck unsuitable for cisplatin-based chemoradiation. This study evaluated using docetaxel as a radiosensitizer. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 were randomly assigned (1:1) to receive either radiation therapy alone or with concurrent docetaxel (15 mg/m2) once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). Most patients (about 60%) received the treatment as definitive. Cisplatin ineligibility was defined by multiple parameters, including an ECOG PS of 2, calculated creatinine clearance <50 mL/min, and organ dysfunction of grade 2 or higher. A total of 356 patients were enrolled (176 in the radiation therapy arm and 180 in the radiation-and-docetaxel arm).[34]

The 2-year DFS rate was 30.3% in the radiation-alone arm (95% CI, 23.6%–37.4%) and 42% in the radiation-and-docetaxel arm (95% CI, 34.6%–49.2%) (HR, 0.673; 95% CI, 0.521–0.868; P = .002).

A phase III randomized trial in India included patients with locally advanced SCC of the head and neck unsuitable for cisplatin-based chemoradiation. This study evaluated using docetaxel as a radiosensitizer. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 were randomly assigned (1:1) to receive either radiation therapy alone or with concurrent docetaxel (15 mg/m2) once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). Most patients (about 60%) received the treatment as definitive. Cisplatin ineligibility was defined by multiple parameters, including an ECOG PS of 2, calculated creatinine clearance <50 mL/min, and organ dysfunction of grade 2 or higher. A total of 356 patients were enrolled (176 in the radiation therapy arm and 180 in the radiation-and-docetaxel arm).[34]

The corresponding median OS was 15.3 months in the radiation-alone arm (95% CI, 13.1–22.0) and 25.5 months in the radiation-and-docetaxel arm (95% CI, 17.6–32.5) (log-rank P = .035). The 2-year OS rate was 41.7% in the radiation-alone arm (95% CI, 34.1%–49.1%) and 50.8% in the radiation-and-docetaxel arm (95% CI, 43.1%–58.1%) (HR, 0.747; 95% CI, 0.569–0.980; P = .035).[34][Level of evidence A1]

A phase III randomized trial in India included patients with locally advanced SCC of the head and neck unsuitable for cisplatin-based chemoradiation. This study evaluated using docetaxel as a radiosensitizer. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 were randomly assigned (1:1) to receive either radiation therapy alone or with concurrent docetaxel (15 mg/m2) once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). Most patients (about 60%) received the treatment as definitive. Cisplatin ineligibility was defined by multiple parameters, including an ECOG PS of 2, calculated creatinine clearance <50 mL/min, and organ dysfunction of grade 2 or higher. A total of 356 patients were enrolled (176 in the radiation therapy arm and 180 in the radiation-and-docetaxel arm).[34]

There was a higher incidence of grade 3 or higher mucositis (22.2% vs. 49.7%; P < .001), odynophagia (33.5% vs. 52.5%; P < .001), and dysphagia (33% vs. 49.7%; P = .002) for patients who received radiation and docetaxel versus radiation alone.

A phase III randomized trial in India included patients with locally advanced SCC of the head and neck unsuitable for cisplatin-based chemoradiation. This study evaluated using docetaxel as a radiosensitizer. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 were randomly assigned (1:1) to receive either radiation therapy alone or with concurrent docetaxel (15 mg/m2) once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). Most patients (about 60%) received the treatment as definitive. Cisplatin ineligibility was defined by multiple parameters, including an ECOG PS of 2, calculated creatinine clearance <50 mL/min, and organ dysfunction of grade 2 or higher. A total of 356 patients were enrolled (176 in the radiation therapy arm and 180 in the radiation-and-docetaxel arm).[34]

The increase of toxicity observed in the radiation-and-docetaxel arm did not significantly impair the total radiation dose the patients received. A total of 88.9% of patients in the radiation-and-docetaxel arm and 93.8% of patients in the radiation-alone arm received the total radiation dose. In the radiation-and-docetaxel arm, 85.6% of patients received five or more cycles of chemotherapy.

In a randomized trial of patients with locally advanced head and neck cancer, curative-intent radiation therapy alone (213 patients) was compared with radiation therapy plus weekly cetuximab (211 patients).[35] The initial dose of cetuximab was 400 mg/m2 of body-surface area 1 week before radiation therapy was started, followed by a weekly dose of 250 mg/m2 of body-surface area for the duration of the radiation therapy. This study allowed altered-fractionation regimens to be used in both arms.[35,36][Level of evidence A1]

In a randomized trial of patients with locally advanced head and neck cancer, curative-intent radiation therapy alone (213 patients) was compared with radiation therapy plus weekly cetuximab (211 patients).[35] The initial dose of cetuximab was 400 mg/m2 of body-surface area 1 week before radiation therapy was started, followed by a weekly dose of 250 mg/m2 of body-surface area for the duration of the radiation therapy. This study allowed altered-fractionation regimens to be used in both arms.[35,36][Level of evidence A1]

At a median follow-up of 54 months, patients treated with cetuximab and radiation therapy demonstrated significantly higher progression-free survival (PFS) (HRdeath or for disease progression, 0.70; P = .006).

In a randomized trial of patients with locally advanced head and neck cancer, curative-intent radiation therapy alone (213 patients) was compared with radiation therapy plus weekly cetuximab (211 patients).[35] The initial dose of cetuximab was 400 mg/m2 of body-surface area 1 week before radiation therapy was started, followed by a weekly dose of 250 mg/m2 of body-surface area for the duration of the radiation therapy. This study allowed altered-fractionation regimens to be used in both arms.[35,36][Level of evidence A1]

Patients in the cetuximab arm experienced higher rates of acneiform rash and infusion reactions, although the incidence of other grade 3 or higher toxicities, including mucositis, did not differ significantly between the two groups.