Toshiyuki Kokatsu

Induction chemotherapy in advanced head and neck cancer.

Induction chemotherapy, followed by definitive treatment, was performed in patients with advanced squamous-cell carcinoma of the head and neck. In this study, carried out between 1984 and 1991, testing the effectiveness of multimodality therapy in patients with previously untreated advanced (stage III and IV) squamous-cell carcinoma of the pharynx, patients received two different induction chemotherapy regimens: cisplatin, vincristine (Oncovin) plus peplomycin (COP), and cisplatin plus continuous 120-hr 5-fluorouracil (5-FU) infusion (CF) for two courses. Overall response rates (complete response plus partial response) to each of the two induction chemotherapy regimens were high: 76 and 82%, respectively. Superior complete response rate in the group receiving CF therapy was 16% versus 10% for COP therapy. Responders to induction chemotherapy had significantly better survival compared with non-responders. The toxicity of these two regimens was tolerable and manageable. It is indispensable to develop the more efficacious chemotherapy regimen with the potential to induce complete disappearance of tumors in patients with advanced head and neck carcinomas.

Chemotherapy for recurrent adeno- and adenoidcystic carcinomas in the head and neck

We have investigated the effectiveness of chemotherapy for patients with recurrent adeno- and adenoidcystic carcinomas in the head and neck. Fourteen cases received a monthly combination chemotherapy regimen of cyclophosphamide, pirarubicin and cisplatin (CAP therapy). A response rate of 36% (5/14) was achieved. There was one complete response and four partial responses. The median duration of response was 37 months in the complete response case and 16 months (range, 6 to 20) in the partial response cases. The toxicity of this chemotherapy was acceptable. The result demonstrates that CAP therapy is an effective regimen for adeno- and adenoidcystic carcinomas. It may also be available as induction or adjuvant chemotherapy for patients with advanced tumors of these cancers.

Clinical application of recombinant human erythropoietin for treatments in patients with head and neck cancer

SummaryThe therapeutic effects of intravenous recombinant human erythropoietin (r-hEPO) administration on anemia induced by radiation therapy (3 cases), chemotherapy (18 cases) and combined therapies (5 cases) in patients with head and neck malignancies were examined. The effectiveness was evaluated by the changes in the hemoglobin concentration examined before and after the r-hEPO administration. The r-hEPO administration combined with anticancer therapies improved anemia induced by all three treatments. The therapeutic effectiveness of r-hEPO injection was also noted on anemia induced by all of four different chemotherapeutic regimens that have been ordinarily used for head and neck malignancies. Furthermore, the efficacy of the different dose schedules, 3000 IU (12 cases) or 6000 IU (14 cases), three times a week, was compared. Both of the r-hEPO dose schedules were effective for anemia, but the efficacy of 6000 IU was superior to that of 3000 IU. No significant changes were observed in the number of white blood cells and platelets and the results of biochemical examinations after the r-hEPO injection. There were no objective side-effects related to the r-hEPO administration. These results suggest that anemia induced by chemotherapy and/or radiotherapy could be prevented by r-hEPO administration. The addition of r-hEPO to anticancer therapies would make it possible to pursue the planned therapeutic schedules, prevent the decrease of immunity after allogeneic blood transfusion and bring about an improvement in the prognosis of patients with malignancies.

Comparison of granisetron alone and granisetron plus hydroxyzine hydrochloride for prophylactic treatment of emesis induced by cisplatin chemotherapy

The efficacy and safety of granisetron alone (group G) and granisetron plus hydroxyzine hydrochloride (group G/H) as prophylactic therapy for acute and delayed nausea and vomiting were evaluated in an open trial in head and neck cancer patients undergoing chemotherapy with cisplatin. The severity of nausea was significantly reduced on days 1 and 4 in patients receiving combination therapy, but the frequency of vomiting was not significantly different between the two groups. The only side-effect observed was headache in 1 patient from group G, and no drug-related laboratory test abnormalities were observed. These results suggest that the anti-emetic efficacy of granisetron can be augmented by hydroxyzine hydrochloride.

Effectiveness of weekly subcutaneous recombinant human erythropoietin administration for chemotherapy-induced anemia

The effects of weekly subcutaneousrecombinant human erythropoietin (r-hEPO)administration on anemia during chemotherapy includingcisplatin and 5-fluorouracil in patients with head andneck carcinomas were examined. Weekly subcutaneousr-hEPO administration in cancer patients has not beeninvestigated previously. Patients were treated withr-hEPO 100 IU/kg (2 patients), 200 IU/kg (6 patients),or 400 IU/kg (5 patients), or placebo, andeffectiveness was evaluated by monitoring hemoglobinconcentration changes after administration for 8weeks. Hemoglobin concentrations in all 3 r-hEPOdosage groups were higher than that in the controlgroup during chemotherapy. All r-hEPO doses producedimprovements in the anemia induced by chemotherapy;however, the 400 IU/kg dose was most effective. Therequirement for blood transfusions decreased inpatients receiving r-hEPO therapy, and no significantside-effects were associated with r-hEPOadministration. These results suggest thatchemotherapy-induced anemia can be prevented by weeklysubcutaneous r-hEPO administration.

Modified Combination Chemotherapy of Cisplatin and 5-Fluorouracil in Squamous Cell Carcinomas of the Head and Neck

Randomized studies on the efficacy of two courses of different types of chemotherapy, including cisplatin and 5-fluorouracil (5-FU), were performed on 130 previously untreated cases with advanced squamous cell carcinomas of the head and neck. Cisplatin, followed by 120-hr continuous 5-FU infusion given in the conventional way, was administered to 60 patients (Group A), while cisplatin was administered 72 hr after the initiation of continuous 5-FU infusion in 70 other patients (Group B). The overall response rates (complete response plus partial response) were 58% in group A and 69% in group B, respectively. A superior complete response rate was obtained in cases receiving modified chemotherapy (10% in group A vs 20% in group B). There was no significant difference in the incidence of side effects between the two groups. These findings indicate that the modified cisplatin plus 5-FU combination chemotherapy tested here is more efficacious regimen than that of the conventional one to achieve high complete response rate and subsequently, to improve the survival of advanced carcinoma cases of the head and neck.

Hypopituitarism and hyponatremia in a case with nasopharyngeal carcinoma.

We report a case of nasopharyngeal carcinoma (NPC) accompanied by hyponatremia and polyuria which was induced by tumor invasion into the pituitary gland. Magnetic resonance imaging showed the pituitary gland pushed upward by NPC. Hypopituitarism due to an intracranial tumor and the extracellular volume excess due to chemotherapy caused hyponatremia and polyuria. As the intracranial tumor was diminished by chemotherapy and irradiation, pituitary hormones were normalized. In patients with T4 NPC, pituitary-adrenocortical function should be endocrinologically evaluated before treatment.

Secretion of a Fibronectin-Like Substance from Head and Neck Carcinomas

The secretion of a fibronectin-like substance in culture supernatants of cell lines of head and neck squamous cell carcinomas was observed. Culture supernatants of some tumor cells had a high cell-attachment activity. Enzyme-linked immunosorbent assay with an antifibronectin antibody showed that the supernatant with cell attachment activity contained fibronectin. Furthermore, the cell attachment activity was clearly inhibited by the addition of a monoclonal antibody to fibronectin. These findings strongly suggest that the fibronectin produced by cancer cells is one of the potent mediators of the cell attachment.