Treatment of Locally Advanced Head and Neck Cancer: Historical and Critical Review

Muhyi Al-Sarraf, MD, FRCPC, FACP

Cancer Control. 2002;9(5)

Conclusions

Considerable progress has been made in the treatment results of patients with locally advanced head and neck cancers. This has resulted in a decrease in distant involvement and improvements in local control, quality of life (with organ preservation), disease-free survival, and overall survival. These endpoints have been demonstrated not only in carefully designed phase III trials and meta-analyses, but also -- and more significantly -- in the changes in the natural history of this disease as shown on the national level, especially in patients with advanced nasopharyngeal cancer. The use of "total" chemotherapy-radiation therapy treatment, the appropriate application of the newer chemotherapy active agents, and the inclusion of the biological and the specific targeted compounds as part of therapy in these patients should provide further improvement in treatment outcomes.

This article was originally certified for CME credit. For accreditation details, contact the publisher.
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Address reprint requests to Muhyi Al-Sarraf, MD, William Beaumont Hospital, 3577 W. 13 Mile Road, #404, Royal Oak, MI 48073. E-mail: mealsarraf@aol.com

No significant relationship exists between the author and the companies/organizations whose products or services may be referenced in this article.

Cite this: Treatment of Locally Advanced Head and Neck Cancer: Historical and Critical Review - Medscape - Sep 01, 2002.

Table 1. Annual Change in Death Rates Between 1990-1997 for Selected Tumor Types and Patients
Sites	Mortality Rate (% Change)
All	-0.8
Melanoma	+0.1
Non-Hodgkin's lymphoma	+1.7
Urinary bladder	-0.3
Lung	-0.5
Colon/rectum	-1.8
Female breast	-2.1
Prostate	-2.2
Oral cavity/pharynx	-2.6
Men	-2.8
White	-2.6
Black	-3.8
Women	-2.3
White	-2.3
Black	-2.5

Table 2. Possible Mechanisms of Interaction Between Chemotherapy and Radiation Therapy
Modification of the slope of the dose-response curve.
Decrease in accumulation or inhibition of repair of sublethal damage.
Inhibition of repair of potentially lethal damage.
Induction of tumor re-oxygenation.
Selective cytotoxicity and/or radiosensitization of hypoxic cells.

Table 2. Possible Mechanisms of Interaction Between Chemotherapy and Radiation Therapy
Modification of the slope of the dose-response curve.
Decrease in accumulation or inhibition of repair of sublethal damage.
Inhibition of repair of potentially lethal damage.
Induction of tumor re-oxygenation.
Selective cytotoxicity and/or radiosensitization of hypoxic cells.

Table 2. Possible Mechanisms of Interaction Between Chemotherapy and Radiation Therapy
Modification of the slope of the dose-response curve.
Decrease in accumulation or inhibition of repair of sublethal damage.
Inhibition of repair of potentially lethal damage.
Induction of tumor re-oxygenation.
Selective cytotoxicity and/or radiosensitization of hypoxic cells.

Table 3. Meta-analysis of Concurrent Chemoradiotherapy vs Radiotherapy in Patients With Advanced Head and Neck Cancers: Mortality
Stratum and Treatment	Risk Difference (%)	P Value*
Overall results	11	<.00001
Conventional RT both arms	9.2	.00041
RT same both arms, not conventional	16.6	.00008
Platinum-based CT	12.1	<.0001
Mitomycin-C based CT	14	.032
5-Fluorourcil-based CT	10.2	.11
Bleomycin-based CT	5	.36
Single agents only	10.7	.0004
Combination CT regimens	11.2	.0009
Combination cisplatin-5FU	15.3	<.0001

Table 4. Phase III Randomized Trials Comparing Concomitant Chemotherapy-Radiation Therapy vs Radiation Therapy Alone in Squamous Cell Head and Neck Cancers
Authors	Site	Treatment	Overall Survival (%)	Year	P Value
Merlano et al^[18]	All	RT	10	5	<.05
		RT, PF	24
Brizel et al^[19]	All	RT bid	34	3	.07
		RT, PF	55
Wendt et al^[20]	All	RT bid, PF	24	3	<.05
		RT bid, PF	49
Calais et al^[21]	Oropharynx	RT bid	31	3	<.05
		RT bid, CF	51
Jeremic et al^[22]	All	RT bid	25	5	.0075
		RT bid, P daily	46
Adelstein et al^[23]	All	RT	20	3	.016
		RT, P	37
		RT, PF ± S	29
Staar et al^[24]	Oropharynx/hypopharynx	RT bid	39	2	.09
		RT bid, CF	44

Table 5. Survival in Nonrandomized Studies of Treatment of Previously Untreated Nasopharyngeal Cancer
Therapy	No. of Series	Patients Studied	Range	% Surviving (Average)
RT only	18	8,185	26-62	45
CT RT	10	683	35-78	62
CT RT	4	172	55-94	67
RT CT	3	85	50-77	66
CT + RT CT	3	162	70-80	77
CT CT + RT	2	65	83-94	88

Table 6. Response to Chemotherapy in Metastatic/Recurrent and Previously Untreated Nasopharyngeal Cancer
Agents	No. of Series	Total Patients	% Response Rate		% Complete Response
Agents	No. of Series	Total Patients	Range	Average	Range	Average
Metastatic/recurrent:
No P	2	38	40-50	45	0-12	6
No PF	4	145	50-63	56	16-20	17
PF	7	221	38-86	65	4-25	16
PT	3	73	57-75	64	3-14	9
Previously untreated:
No P	1	12	81		33
No PF	6	265	75-98	86	5-66	33
PF	9	428	62-100	87	10-50	30

Table 5. Survival in Nonrandomized Studies of Treatment of Previously Untreated Nasopharyngeal Cancer
Therapy	No. of Series	Patients Studied	Range	% Surviving (Average)
RT only	18	8,185	26-62	45
CT RT	10	683	35-78	62
CT RT	4	172	55-94	67
RT CT	3	85	50-77	66
CT + RT CT	3	162	70-80	77
CT CT + RT	2	65	83-94	88

Table 7. Randomized Trials in Patients With Nasopharyngeal Cancers
	Authors	Agents	Overall Survival	P Value	Comments
Adjuvant	Rossi et al^[29]	CAV	67% RT	NS
			59% RT-VCA
	Chi et al^[30]	PF-L	61% RT-CT	NS
			55% RT
Induction	VUMCA^[32,33]	PEB	40% CT-RT	NS
			45% RT
	Chau et al^[34]	PE	70% CT-RT	NS
			56% RT
	Ma et al^[37]	PFB	63% CT-RT	NS	RFS P = .05, FLR P = .04
			56% RT
	Hareyamam et al^[38]	PF	60% CT-RT	NS	DFR 74%
				48% RT	56%
Concurrent	Chan et al^[39]	P	76% CT-RT	.1	T3* 68% P=.0075
Concurrent			69% RT	46%
Induction/Adjuvant	Chan et al^[31]	PF	80% CT-RT	NS
Induction/Adjuvant			81% RT
Concurrent/Adjuvant	Al-Sarraf et al^[35,36]	P/PF	67% CT-RT	<.001	DRS 74%
Concurrent/Adjuvant			37% RT	46%

Table 8. Stage IV Nasopharyngeal Cancer: Change in Overall Survival, 1980-2000
Treatment	% 5-Year Survival
RT without salvage	<30
RT with salvage	±40
Concurrent CT + RT	50-55
Sequential CT RT	50-55
RT CT	50-55
CT + RT CT	75
CT CT + RT	>90

Table 9. Targeted Therapy With or Without Chemotherapy in Metastatic/Recurrent Head and Neck Cancers
Author	Agent	Chemotherapy	No. of Patients	Evaluable	Complete Response	Partial Response	% Response Rate
Hong et al^[43]	C225	P	38	38	1	7	21
Baselga et al^[46]	C225	P/C	96	96	2	12	15
Burtness et al^[47]	C225	P	60	57	3	9	21
Burtness et al^[47]			P	6358239
Senzer et al^[49]	SI-774		114	78		10	13
Cohen et al^[45]	D-1839		52	47	1	4	11
Kies et al^[44]	CH-66336		17	17		3	18
Zahalsky et al^[47]	SU-5416		27	20	1		5

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Treatment of Locally Advanced Head and Neck Cancer: Historical and Critical Review

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