The authors discuss the results of 3 studies of their group reflecting the possible role of amifostine in simultaneous radiochemotherapy (RCT) of advanced head and neck cancer. In a controlled phase II trial (1995 through 1996), 39 patients were included in this pilot investigation. A control group (n = 14) received simultaneous RCT of the head and neck region with an irradiation dose of 60 Gy and 2 cycles of carboplatin (700 mg/m(2) cumulative dose). Twenty-five patients received the same basic therapy and an additional 500-mg dose of amifostine before each chemotherapy. Amifostine was administered less than 45 minutes before the end of radiotherapy. The authors observed a dramatic reduction of typical radiotherapy-associated toxicities (mucositis, xerostomia, loss of taste, dysphagia). The hematologic side effects (leukocytopenia, anemia, thrombocytopenia) also were decreased significantly. The overall survival rate and locoregional control of both groups were comparable after 12 months. In a controlled intensification trial (1997 through 1999), the authors included 76 consecutive patients (69 men, 7 women) with pharyngeal cancer (oropharynx, n = 33; hypopharynx, n = 43). The tumors were characterized as unresectable and locally advanced without distant metastasis. All patients received a conventional radiotherapy (2-Gy single dose, daily fractionation) up to doses of 60 Gy and an additional 10 Gy as a boost in the tumor-infiltrated region. A dose of carboplatin, 70 mg/m(2), was given to a group of 45 patients on days 1 through 5 and 29 through 33 of radiotherapy (RCT arm). The resulting cumulative dose was 700 mg/m(2). A group of 31 patients (RCTintens arm) received the same dose of carboplatin on days 1 through 5, 22 through 26, and 43 through 47 or 1 through 5, 15 through 19, 29 through 33, and 43 through 47 of radiotherapy (cumulative dose 1.05 to 1.40 mg/m(2)). All patients received 500 mg of amifostine before each carboplatin administration. If the tumor volume was less than 20 cm(3), we observed an increased 1-year overall survival rate (91% v 71%) and time to progression (17 months v 10 months). If the tumor volume was greater than 20 cm(3), we observed comparable treatment results in both groups (1-year survival rate, 60% v 61%; time to progression, 13 months v 12 months). In a long-term follow-up investigation (1999 through 2000), 531 patients (89 women, 442 men) were analyzed according to their toxicities during regular follow-up investigations at our outpatient facility. All patients were treated by surgery or radio(chemo)therapy because of an advanced head and neck cancer. A total of 218 of 531 patients received the antineoplastic therapy without cytoprotection. An additional 313 patients received their RCT combined with amifostine administration before administration of the radiosensitizer. A significant influence of cytoprotection was registered in the following toxicities: xerostomia, fibrosis, loss of taste, and dysphagia. No impact was seen on the development of interstitial lymph edema and esophageal stenosis. Amifostine could be integrated in simultaneous radiochemotherapy of advanced head and neck cancer patients. The authors favor the administration of amifostine before chemotherapeutics alone. Selective cytoprotection could decrease the main acute toxicities (mucositis, xerostomia, dysphagia) as well as late side effects (xerostomia, loss of taste, fibrosis) of this form of combined treatment. The enhanced therapeutic index may be changed into a prognostic benefit for selected patients with unresectable tumors, if the volume is smaller than 20 cm(3).

Anthracyclines are wel known as effective chemotherapeutical agents in the treatment of head and neck cancer. We report about the results of two consecutive phase-II-studies investigating the effects of a new liposomal doxorubicin formulation in the therapy of advanced cancers in the ENT region. 25 patients received a palliative monochemotherapy (A) with 25 mg/sqm BSA liposomal doxorubicin every 3 weeks. Following results were seen: Total response rate 45 %, median survival 9 month, time to progression 8 month, 1-year-overall survival 34 %. Further 15 patients (B) received 20 mg/sqm BSA liposomal doxorubicin every 3 weeks simultaneously to an irradiation of the tumour area. Tn this group we have seen the following results: Total response rate 87 %, median survival 18 month, timt to progression 17 month, 1-year overall survival 57 %. No severe toxicities were registered in group A, group B showed an enhancement of typical radiological side effects.

PURPOSE:The radiotherapeutic possibilities are limited for patients with a recurrent or second head and neck cancer if the patient was already irradiated in the first therapy. In the presented study we investigated the changes of this situation due to the usage of amifostine in the case of re-irradiation (simultaneous radio-chemotherapy).PATIENTS AND METHODS:Between 1995 and 1997 we treated 14 patients with a recurrent or second malignancy of the head and neck region by a simultaneous radio-chemotherapy (20 x 1.5 Gy, Carboplatin 70 mg/m2 BSA on days 1 to 5 and 16 to 20, 500 mg amifostine prior to every carboplatin infusion). Six out of 14 patients got an additional brachytherapy (10 to 15 Gy) to increase the local dose because of a residual tumor. In 4 cases the treatment was an adjunctive one, following the surgical tumor debulking.RESULTS:We have seen 3 complete remissions (21.4%), and 8 partial remissions (57.1%). The median time of observation is 13 months now. Three out of 14 patients died, 2 because of the tumor. Hematological toxicities: side effects Grade 2 WHO were seen only in 1 patient. Acute non-hematological toxicities: mucositis Grade 0/1 in 7 patients, mucositis Grade 2 in 7 patients, dysphagia Grade 0/1 in 9 patients, dysphagia Grade 2 in 5 patients, xerostomia Grade 1 in 9 patients, xerostomia Grade 2 in 3 patients. We registrated only 1 serious late toxicity due to radio-chemotherapy: 4 months after brachytherapy a patient (with laryngectomy) developed a submental fistula.CONCLUSION:These first results suggest that the usage of amifostine offers new potential ways for re-irradiation of patients with recurrent or second malignancies in the head neck region.

Purpose: The radiotherapeutic possibilities are limited for patients with a recurrent or second head and neck cancer if the patient was already irradiated in the first therapy. In the presented study we investigated the changes of this situation due to the usage of amifostine in the case of re-irradiation (simultaneous radio-chemotherapy). Patients and Methods: Between 1995 and 1997 we treated 14 patients with a recurrent or second malignancy of the head and neck region by a simultaneous radio-chemotherapy (20 x 1.5 Gy, Carboplatin 70 mg/m(2) BSA on days 1 to 5 and 16 to 20, 500 mg amifostine prior to every carboplatin infusion). Six out of 14 patients got an additional brachytherapy (10 to 15 Gy) to increase the local dose because of a residual tumor. In 4 cases the treatment was an adjunctive one, following the surgical tumor debulking. Results: We have seen 3 complete remissions (21.4%), and 8 partial remissions (57.1%). The median time of observation is 13 months now. Three out of 14 patients died, 2 because of the tumor. Hematological toxicities: side effects Grade 2 WHO were seen only in 1 patient. Acute non-hematological toxicities: mucositis Grade 0/1 in 7 patients, mucositis Grade 2 in 7 patients, dysphagia Grade 0/1 in 9 patients, dysphagia Grade 2 in 5 patients, xerostomia Grade 1 in 9 patients, xerostomia Grade 2 in 3 patients. We registrated only 1 serious late toxicity due to radio-chemotherapy: 4 months after brachytherapy a patient (with laryngectomy) developed a submental fistula. Conclusion: These first results suggest that the usage of amifostine offers new potential ways for re-irradiation of patients with recurrent or second malignancies in the head neck region.

A multimodal organ- and functionpreserving therapy concept in patients with locally advanced carcinoma of the pharynx and supraglottic larynx including laser-surgical resection of the primary tumor (PT), functional neck dissection (ND) and concomitant simultaneous radiochemotherapy (RCT) was introduced in our hospital in 1992. Until December 1996 43 patients treated with this multimodal therapy. These patients achieved a better overall survival and a diminished rate of locoregional recurrence compared with a group of patients receiving conventional radical resection and adjunctive radiotherapy (RT). The laser-surgical procedure of macroscopic removal of the primary tumor is important: the outcome of patients with definitive RCT alone was worse.

Background: Retinoids have been increasingly used since the mid-1960s for the treatment of leukoplakia and dysplasia of the head and neck. Studies of their use in the treatment of carcinomas of the head and neck, usually in combination with interferons, have also been published in recent years. Methods: 30 patients (25 men, five women) with UICC stage IV were given adjunctive treatment with a combination of 3×3 million IU of interferon alfa SC weekly and 0.5 mg/kg body weight of 13-cis retinoic acid PO daily for a maximum duration of 6 months. The therapeutic benefits and side effects are reported here. Results: Therapy was completed as scheduled in 16 out of 30 patients. Reasons for stopping treatment: progressive disease (ten patients), side effects (four patients). 18 patients were tumor-free following treatment. 16 patients displayed a complete response one year after completion of adjunctive treatment. Retinoic-associated side effects observed included xerostomia (90%), dysphagia (67%), weight loss (50%), flush (50%) and cachexia (7%). Interferon-associated side effects included pyrexia and moderate hematological changes. Conclusion: Adjunctive combination treatment with interferon alfa and 13-cis retinoic acid appears to be beneficial to patients with head and neck cancer. The side effects are moderate.

Amifostine, an organic thiophosphate, has been shown to protect normal tissues from the effects of chemo- and radiotherapy without loss of anti-tumour activity. Based on previous work (11), we explored amifostine's role in allowing intensification of a concurrent radiochemotherapy regimen. This standard of irradiation was 2 Gy single dose, 70 Gy total dose; carboplatin was administered on the days of week 1 and 5 prior to the radiation (cumulative dose 700 mg/sqm BSA). If carboplatin was combined with 5-FU (6000 mg/sqm BSA prolonged infusion) the incidence of mucositis and dysphagia increased already in week 3-4, if the total dose of carboplatin alone was increased up to 1.400 mg/sqm BSA the hematological and nonhematological toxicities remain on the lower level until week 6. On the base of these results we favour the second way ("high-dose carboplatin") in intensifying the standard treatment.

Background: Amifostine has reduced toxicities associated with radiation therapy and platinum-based chemotherapy. In a phase II randomized trial, we investigated the ability of amifostine to reduce the toxicity of carboplatin plus radiotherapy (RCT) in patients with head and neck cancer.Patients and methods: Thirty-nine patients with stage III or IV squamous cell carcinomas of the head and neck received RCT (following surgery or as primary treatment). Radiotherapy was given five days per week with daily fractions of 2 Gy, up to a total dose of 60 Gy in conjunction with carboplatin 70 mg/m(2) on days 1 through 5 and days 21 through 26. Eligible patients were randomised to receive RCT alone or preceded by a rapid infusion of amifostine (500 mg) on the days when carboplatin was administered.Results. Patients receiving amifostine + RCT (II = 25) had significantly reduced mucositis (P = 0.0001) and xerostomia (P = 0.0001) in comparison with patients receiving RCT alone (n = 14). Additionally, patients receiving amifostine + RCT had significantly less thrombocytopenia (P = 0.001) and leukopenia (P = 0.001). At 12 months following therapy, 79% of patients receiving amifostine + RCT had no evidence of disease compared with 64% of those receiving RCT alone.Conclusions: Amifostine reduces the RCT-induced toxicities in patients with head and neck cancer and has no negative impact on antitumour efficacy.

The role of tumor markers in the long-term follow-up of patients with head and neck tumors is highly controversial. The following paper presents a retrospective analysis of the time course of the markers SCC, CEA and NSE in 100 assessable patients out of a total of 142 patients with squamous cell carcinoma of the head and neck. The sensitivities of the respective substances on their own were very low (SCC 41.2%, CEA 32.3%, NSE 67.6%). A sensitivity of 91.2% was only obtained by combining the markers SCC and NSE. However, the specificity of this combination is fairly low (60.9%). The importance of NSE resides in its high degree of sensitivity in patients with remote metastases. The additional determination of CEA is of no added diagnostic benefit. A rise in tumor markers was the first sign of progressive disease in 32.4% of patients with recurrent disease. No therapeutic benefit can at present be derived from the time gained.On balance, determination of the named tumor marker combination is a reliable, non-invasive, clinically enhancing aid in the long-term follow-up of patients with carcinomas of the head and neck.