Analyses of Distant Metastases in Squamous Cell Carcinoma of the Head and Neck and Lesions Above the Clavicle at Autopsy

Nishijima, Wataru; Takooda, Shoji; Tokita, Nobuhiro; Takayama, Shojiro; Sakura, Mizuyoshi

doi:10.1001/archotol.1993.01880130067009

Cited by 106 publications

(54 citation statements)

References 7 publications

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“…5 In one of the studies, animals (n = 3 per sex per group) had been treated by once weekly i.v. administration for 6 weeks followed by a 4-week recovery period at doses of 0.5, 1.5, and 4 mg/kg.…”

Section: Bivatuzumab Bivatuzumab Mertansine and Cd44v6mentioning

confidence: 99%

“…To this end, archival tumor biopsies of the patients, obtained at earlier presentation of the patient at the clinic, were stained for CD44v6 expression. Staining was done using the streptavidin-biotin-immunoperoxidase technique with the murine antiCD44v6 mAb BIWA 1 (also designated VFF18, Bender Med Systems, 5 Unpublished data. …”

Section: Immunohistochemical Staining Of Tumor Tissuesmentioning

confidence: 99%

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A Phase I Dose Escalation Study with Anti-CD44v6 Bivatuzumab Mertansine in Patients with Incurable Squamous Cell Carcinoma of the Head and Neck or Esophagus

Tijink

Buter

Bree

et al. 2006

Clinical Cancer Research

269

208

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Purpose: To assess safety, pharmacokinetics, maximum tolerated dose, and preliminary efficacy of bivatuzumab mertansine. Bivatuzumab is a humanized monoclonal antibody directed against CD44v6, which previously seemed to be safe in phase I radioimmunotherapy trials, whereas the conjugated mertansine is a potent maytansine derivative. Experimental Design: Patients with incurable squamous cell carcinoma of the head and neck or esophagus were eligible. Bivatuzumab was given weekly for 3 consecutive weeks by i.v. infusion. One patient was planned to be treated at each dose tier as long as toxicity did not reach grade 2; otherwise, three patients had to be treated until dose-limiting toxicity occurred. Starting dose was 20 mg/m 2 and dose was subsequently escalated in steps of 20 mg/m 2 . Patients without diseaseprogression and not experiencing dose-limiting toxicity were eligible for repeated courses. Blood serum samples were taken throughout the treatment period to determine the pharmacokinetic properties of bivatuzumab mertansine and to assess the human anti^bivatuzumab mertansine antibody response. Results: Seven patients received a total of 23 weekly doses of bivatuzumab mertansine. One patient at the 100 mg/m 2 and one at the 120 mg/m 2 level experienced stable disease during treatment phase but also developed grade 1skin toxicity (desquamation). One of them received a second treatment course. At the highest dose level achieved in this study (140 mg/m 2 ), one patient developed toxic epidermal necrolysis after two infusions and died. Massive apoptosis of skin keratinocytes had occurred, whereas only symptomatic therapy for skin toxicity was available. The riskbenefit assessment of all patients treated in the total phase I program (4 clinical trials, 70 patients) turned out to be negative after consideration of this case of a toxic epidermal necrolysis and the skin-related adverse events observed in the other trials.Therefore, development of the conjugate was discontinued. Interindividual variability in pharmacokinetic variables was low and exposure to BIWI 1 increased proportionally with dose. No anti^bivatuzumab mertansine reactions were observed. Conclusion: The main toxicity of bivatuzumab mertansine was directed against the skin, most probably due to CD44v6 expression in this tissue. The majority of skin reactions was reversible; however, one fatal drug-related adverse event had occurred. Clinical development was discontinued before reaching maximum tolerated dose.

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Section: Bivatuzumab Bivatuzumab Mertansine and Cd44v6mentioning

confidence: 99%

Section: Immunohistochemical Staining Of Tumor Tissuesmentioning

confidence: 99%

A Phase I Dose Escalation Study with Anti-CD44v6 Bivatuzumab Mertansine in Patients with Incurable Squamous Cell Carcinoma of the Head and Neck or Esophagus

Tijink

Buter

Bree

et al. 2006

Clinical Cancer Research

269

208

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“…Metastasis in any lymph node other than regional is classified as a distant metastasis. Clinical data report an incidence of 4.2-23.8% of distant metastases prevalently in SCC (table 1) [11,[14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and about 37.7-58.8% in ACC in all salivary sites [20,24,28,30], while autopsy studies have demonstrated the incidence of distant metastasis to be as high as 57% in SCC (table 2) [31][32][33][34][35][36][37][38][39][40][41][42][43]. Kotwall et al [41], in their study, noted that hypopharynx had the highest incidence of distant metastases (60.1%), followed by the base of the tongue (52.7%) and the anterior tongue (49.4%).…”

mentioning

confidence: 99%

Incidence and Sites of Distant Metastases from Head and Neck Cancer

Ferlito

Shaha

Silver

et al. 2001

ORL

348

248

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The incidence of distant metastases in head and neck squamous cell carcinoma (SCC) is relatively small in comparison to other malignancies. Distant metastases adversely impact survival and may significantly affect treatment planning. The incidence of distant metastases is influenced by location of the primary tumor, initial T and N stage of the neoplasm, and the presence or absence of regional control above the clavicle. Patients with advanced nodal disease have a high incidence of distant metastases, particularly in the presence of jugular vein invasion or extensive soft tissue disease in the neck. Primary tumors of advanced T stages in the hypopharynx, oropharynx and oral cavity are associated with the highest incidence of distant metastases. Pulmonary metastases are the most frequent in SCC, accounting for 66% of distant metastases. It may be difficult to distinguish pulmonary metastasis from a new primary tumor, particularly if solitary. Other metastatic sites include bone (22%), liver (10%), skin, mediastinum and bone marrow. An important question remains as to how intensely pre- and postoperative screening for distant metastases should be performed. Preoperative chest X-ray is warranted in all cases. If the primary tumor and nodal status place the patient at high risk for pulmonary metastasis, then preoperative computed tomography scan of the chest should be done. Screening for distant metastases at other sites is usually not indicated in SCC of the upper aerodigestive tract. Postoperatively, annual X-rays of the chest are usually sufficient, but in high-risk situations a chest X-ray performed every 3–6 months may be beneficial. Certain histologic types of primary tumor have greater or lesser propensity to metastasize distantly, and have a different natural history. Adenoid cystic carcinoma metastasizes frequently, even in the absence of extensive local or regional disease. Basaloid squamous cell carcinoma and neuroendocrine carcinomas also metastasize widely. Extensive evaluation for distant metastases is justified for these tumors. Knowledge of the natural history of various neoplasms and the factors that contribute to distant metastases as well as good judgement are essential for cost-effective treatment planning and decision-making with regard to pre- and postoperative evaluation for distant metastases in cancer of the head and neck.

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“…Nishijima 16 found distant metastases in 41 (37%) of 112 postmortems performed on patients who had head and neck cancer, with the majority occurring within the lung (85%). However, the proportion of synchronous tumors which are metastatic is unknown.…”

Section: Discussionmentioning

confidence: 99%

Role of chest ct scanning in the management of patients presenting with head and neck cancer

et al. 1998

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Analyses of Distant Metastases in Squamous Cell Carcinoma of the Head and Neck and Lesions Above the Clavicle at Autopsy

Cited by 106 publications

References 7 publications

A Phase I Dose Escalation Study with Anti-CD44v6 Bivatuzumab Mertansine in Patients with Incurable Squamous Cell Carcinoma of the Head and Neck or Esophagus

A Phase I Dose Escalation Study with Anti-CD44v6 Bivatuzumab Mertansine in Patients with Incurable Squamous Cell Carcinoma of the Head and Neck or Esophagus

Incidence and Sites of Distant Metastases from Head and Neck Cancer

Role of chest ct scanning in the management of patients presenting with head and neck cancer

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