- After patients with recurrent and / or metastatic squamous cell carcinoma (SCC) of the head and neck have exhausted the options of surgery and / or radiation:
- The likelihood of cure diminishes substantially:
- With a median survival historically being:
- Less than 1 year
- With a median survival historically being:
- The likelihood of cure diminishes substantially:
- In this group, systemic therapy administered with palliative intent is the treatment of choice:
- Single agent therapy can produce objective responses in 10% to 30% of patients:
- Single agents that typically are used in this setting include:
- Cisplatin
- Taxanes
- Methotrexate
- 5-FU
- Cetuximab
- Vinorelbine, bleomycin, ifosfamide, and pemetrexed:
- Also have shown clinical activity against advanced head and neck cancers
- Single agents that typically are used in this setting include:
- Single agent therapy can produce objective responses in 10% to 30% of patients:
- The durability of response to chemotherapy alone:
- Generally is measured in:
- Weeks to months, not years
- Generally is measured in:
- An early, randomized trial reported by Morton:
- Provided evidence that cisplatin treatment prolonged survival:
- By approximately 10 weeks in patients with advanced head and neck cancer:
- Compared with best supportive care
- There are no striking efficacy differences:
- Among cytotoxic chemotherapy agents in the recurrent disease setting:
- Hong and colleagues:
- Compared cisplatin versus methotrexate as palliative therapy for 44 patients with head and neck cancer that had recurred after surgery and / or radiation
- Patients had not received prior chemotherapy
- The median survival was approximately 6 months in both arms:
- Although methotrexate seemed to be somewhat better tolerated
- Hong and colleagues:
- Similarly, in a randomized study of 100 patients with advanced inoperable head and neck cancer:
- That compared cisplatin versus methotrexate:
- Grose and colleagues:
- Did not detect any significant differences in survival between the two treatment groups
- Grose and colleagues:
- That compared cisplatin versus methotrexate:
- Among cytotoxic chemotherapy agents in the recurrent disease setting:
- Taxanes:
- Yielded encouraging response rates as:
- First-line therapy for patients with recurrent disease
- Forastiere’s group:
- Observed a response rate of 40% among 34 patients treated with paclitaxel
- Dreyfuss and colleagues:
- Reported a response rate of 42% among 31 patients treated with docetaxel
- In a randomized phase II trial that compared docetaxel versus methotrexate among 57 patients with advanced head and neck cancer:
- No difference in overall survival was found between the two groups:
- Although the response rate was significantly better for the docetaxel group:
- 27% versus 15%
- Although the response rate was significantly better for the docetaxel group:
- No difference in overall survival was found between the two groups:
- Yielded encouraging response rates as:
- Combination chemotherapy regimens:
- Appear to be associated with:
- Increased response rates and often with increased toxicities:
- But generally not with increased survival
- Increased response rates and often with increased toxicities:
- In 1985 Vogl reported the results of a prospective study:
- In which 163 patients were randomly assigned to receive:
- Methotrexate monotherapy or methotrexate plus bleomycin plus cisplatin
- Objective responses were more frequent in the combination chemotherapy group:
- But median survival was 5.6 months in each group
- In which 163 patients were randomly assigned to receive:
- A three-arm randomized study of 249 patients with advanced head and neck cancer that was reported by Jacobs and colleagues:
- Compared the cisplatin plus 5-FU doublet versus cisplatin monotherapy versus 5-FU monotherapy
- The objective response rate and hematologic toxicities were highest with the doublet regimen:
- But median survival was approximately 5.7 months for all groups
- Taken together, these studies suggest that:
- Combination chemotherapy regimens may be appropriate for patients with good performance status:
- If objective tumor response is believed to be necessary for palliation of advanced head and neck cancer
- No combination chemotherapy regimen appears to be superior to another in terms of survival for patients with advanced head and neck cancer:
- A Southwest Oncology Group study reported by Forastiere randomly assigned 277 patients with advanced head and neck cancer to:
- Treatment with cisplatin plus 5-FU, carboplatin plus 5-FU, or methotrexate monotherapy
- In the comparison of the doublet regimens:
- Cisplatin plus 5-FU yielded a higher response rate than did carboplatin plus 5-FU:
- 32% versus 21%, p = .05
- However, median survival times were similar in all three treatment groups in the study
- Cisplatin plus 5-FU yielded a higher response rate than did carboplatin plus 5-FU:
- A Southwest Oncology Group study reported by Forastiere randomly assigned 277 patients with advanced head and neck cancer to:
- Gibson reported a randomized comparison of cisplatin plus 5-FU (CF) versus cisplatin plus paclitaxel (CP) for 218 patients with advanced head and neck cancer:
- The response rate:
- 27% in the CF group and 26% in the CP group
- Median survival:
- 8.7 months in the CF group and 8.1 months in the CP group
- The overall results did not differ significantly
- 8.7 months in the CF group and 8.1 months in the CP group
- The response rate:
- Combination chemotherapy regimens may be appropriate for patients with good performance status:
- Appear to be associated with:
- Cetuximab represents the first biologic agent to enter routine clinical practice as a palliative agent for patients with advanced head and neck cancer:
- In a phase II study of 103 patients with recurrent and / or metastatic head and neck cancer:
- With documented disease progression within 30 days after a minimum of two and a maximum of six platinum-based chemotherapy treatments:
- Vermorken reported that the:
- Response rate was 13% and the median time to progression was 70 days
- Treatment was generally well tolerated:
- The most common adverse event was a rash
- Vermorken reported that the:
- With documented disease progression within 30 days after a minimum of two and a maximum of six platinum-based chemotherapy treatments:
- In a phase II study of 103 patients with recurrent and / or metastatic head and neck cancer:
- Cetuximab can also be combined with other cytotoxic chemotherapeutic agents to achieve therapeutic advantage for some patients with advanced HNSCC:
- In a phase III study by Burtness for patients with recurrent or metastatic disease who had not received any prior palliative chemotherapy:
- 117 subjects were randomly assigned to receive cisplatin plus cetuximab versus cisplatin plus placebo
- The objective response rate was higher for cisplatin plus cetuximab:
- 26% versus 10%, p = .03:
- But no significant difference in survival was found between the two groups
- 26% versus 10%, p = .03:
- The investigators noted that in the cetuximab plus cisplatin group:
- Objective responses were more frequent in patients who experienced skin toxicity:
- Although the number of subjects was too small to establish a statistically significant correlation between dermatologic toxicity and response
- Objective responses were more frequent in patients who experienced skin toxicity:
- The EXTREME trial randomized 442 patients with untreated recurrent or metastatic head and neck cancer to platinum (cisplatin or carboplatin) plus infusional 5-FU alone for a maximum of 6 cycles with or without cetuximab. Patients randomized to the experimental arm (with cetuximab) with at least stable disease were continued on cetuximab alone after combination therapy. The objective response rate (20% versus 36%, p < .001), progression-free survival (3.3 versus 5.6 months,
- p < .001), and overall survival (7.4 versus 10.1 months, p = .04) all favored the experimental group. The lack of crossover in the study design leaves open the question of whether similar improvements in overall survival could be achieved with sequential treatment with the platinum doublet followed by cetuximab, or vice versa. However, the study does further establish the platinum/5-FU plus cetuximab as a standard first- line palliative option for patients with advanced head and neck cancer.
- One of the most exciting areas of progress for head and neck cancer research is the emergence of immunotherapeutic approaches for this disease, led by the integration of therapeutic antibodies targeting the T cell immune checkpoint PD-1 (pro- grammed death 1) into clinical practice (Fig. 20.18). The activity observed with these drugs established the critical proof of principle that the immune system can be pharmacologically harnessed to produce clinically significant responses in head and neck cancer patients. CHECKMATE-141 was a randomize
- In a phase III study by Burtness for patients with recurrent or metastatic disease who had not received any prior palliative chemotherapy:
Rodrigo Arrangoiz MS, MD, FACS, FSSO 