pirarubicin and Head-and-Neck-Neoplasms

Topics: Antibiotics, Antineoplastic; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Clinical Trials, Phase I as Topic; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Lymphoma; Mesothelioma

Pirarubicin (THP-adriamycin or THP-doxorubicin) was found during a search of new anthracycline antibiotics among 4'-O-substituted compounds having less toxicities than other anthracycline anticancer drugs in 1979 by Umezawa et al. In its preclinical studies, this compound possessed almost similar antitumor efficacies to doxorubicin, but was effective against doxorubicin-resistant P388 and other murine tumor cell lines. This compound was rapidly incorporated into tumor cells, inhibiting DNA polymerase alpha and subsequently DNA synthesis. Inhibition of RNA synthesis was also noted. In the clinical studies, clinical responses were established against head and neck cancer, breast cancer, urogenital cancers, ovarian cancer, uterine cancer, acute leukemia, and malignant lymphoma, showing a wide antitumor spectrum clinically. Among the side effects, cardiac toxicity, alopecia and disturbance of the digestive organs were mild. From these results, THP-adriamycin seems to be a useful clinical drug for human solid tumors.

Topics: Animals; Doxorubicin; Drug Evaluation; Head and Neck Neoplasms; Humans; Lethal Dose 50; Mice

The aim of this study was to evaluate the possible usefulness of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for predicting tumour aggressiveness and response to intra-arterial chemotherapy (THP-ADM + 5-FU + carboplatin) and radiotherapy in head and neck carcinomas. Twenty patients with squamous cell carcinoma (SCC) of the head and neck were included in the study. All patients completed the treatment regimen, and each patient underwent two FDG-PET studies, one prior to and one at 4 weeks after the chemoradiotherapy. For the quantitative evaluation of regional FDG uptake in the tumour, standardised uptake values (SUVs) with an uptake period of 50 min were used. The pre-treatment SUV (pre-SUV) and post-treatment SUV (post-SUV) were compared with immunohistologically evaluated tumour proliferative potential (MIB-1 and PCNA), tumour cellularity and other parameters including histological grade, tumour size and stage, clinical response and histological evaluation after therapy. All neoplastic lesions showed high SUVs (mean, 9.75 mg/ml) prior to the treatment, which decreased significantly after the therapy (3.41 mg/ml, P<0.01). Pre-SUV did not show any correlation with MIB-1, PCNA, cellularity or other parameters. However, lower post-SUV was significantly correlated with good histological results after therapy (no viable tumour cells, n=16). In comparison with moderately differentiated SCCs, well-differentiated SCCs exhibited significantly lower post-SUV and a larger difference between pre- and post-SUVs. Lesions with a high pre-SUV (>7 mg/ml) showed residual tumour cells after treatment in 4 out of 15 patients, whereas patients whose lesions showed a low pre-SUV (<7 mg/ml, five patients) were successfully treated. Four out of six tumours with a post-SUV higher than 4 mg/ml had viable tumour cells, whereas all tumours (14/14) with a post-SUV lower than 4 mg/ml showed no viable tumour cells. Computational multivariate analysis using multiple regression revealed four factors (MIB-1 labelling index, cellularity, the number of MIB-1 labelled tumour cells and tumour size grade) contributing to pre-SUV and pre-post SUV (difference between pre-treatment SUV and post-treatment SUV in each patient) with statistical significance. FDG uptake in the tumour might reflect tumour aggressiveness, which is closely related to the proliferative activity and cellularity. Pre-treatment FDG-PET is useful in predicting the response to treatment, and post-tr

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Combined Modality Therapy; Doxorubicin; Female; Fluorodeoxyglucose F18; Fluorouracil; Follow-Up Studies; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Staging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Tomography, Emission-Computed; Treatment Outcome

To preserve the oral organs and functions in patients with head and neck carcinoma, accurate determination of the appropriate treatment after neoadjuvant chemotherapy and radiotherapy is of critical importance. We evaluated the diagnostic accuracy of (18)F-FDG PET relative to that of other conventional imaging modalities in the assessment of therapeutic response after combined intraarterial chemotherapy and radiotherapy as an organ preservation protocol.. The study was prospectively performed on 23 consecutive patients with head and neck squamous cell carcinoma who completed the treatment regimen and underwent 2 (18)F-FDG PET studies before and after neoadjuvant chemoradiotherapy. (67)Ga scintigraphy (only before therapy) as well as MRI and CT (both before and after therapy) were also performed. All images were blindly and independently interpreted without knowledge of histologic findings. The level of confidence in image interpretation was graded by means of a 5-point rating system (0 = definitely no tumor to 4 = definite tumor).. Before treatment, (18)F-FDG PET detected primary tumors in all 23 patients and was more sensitive (100%) than MRI (18/23; 78.3%), CT (15/22; 68.2%), and (67)Ga scintigraphy (8/20; 40%), with a confidence level of 3 or 4 as a positive tumor finding. After chemoradiotherapy, residual tumors were histologically confirmed in 4 patients (pathologic complete response rate, 19/23; 82.6%). Although posttreatment (18)F-FDG PET showed almost equal sensitivity (4/4; 100%) compared with MRI (3/3; 100%) or CT (3/4; 75%), its specificity (17/19; 89.5%) was superior to MRI (7/17, 41.2%) and to CT (10/17; 58.8%) for primary lesions. Regarding metastases to neck lymph nodes, only specificity for posttreatment images was calculated because no metastasis was confirmed in any patients after treatment. Six subjects had (18)F-FDG PET-positive lymph nodes, which had pathologically no tumor cells and suggested an inflammatory reactive change after therapy. Therefore, the specificity of posttreatment (18)F-FDG PET (17/23; 73.9%) was almost identical to that of MRI (17/20; 85%) and CT (16/21; 76.2%) for neck metastasis. With combined chemoradiotherapy monitored with (18)F-FDG PET, 8 patients avoided surgery and the remaining 15 patients underwent a reduced form of surgery.. (18)F-FDG PET facilitates differentiation of residual tumors from treatment-related changes after chemoradiotherapy, which may be occasionally difficult to characterize by anatomic images. (18)F-FDG PET has a clinical impact for the management of patients with head and neck cancers after neoadjuvant chemoradiotherapy by optimizing surgical treatment for each patient and contributes to the improvement of the patient's quality of life.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Doxorubicin; False Negative Reactions; Female; Fluorodeoxyglucose F18; Fluorouracil; Follow-Up Studies; Gallium Radioisotopes; Head and Neck Neoplasms; Humans; Injections, Intra-Arterial; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Prospective Studies; Radiopharmaceuticals; Radiotherapy, Adjuvant; Reproducibility of Results; Sensitivity and Specificity; Tomography Scanners, X-Ray Computed; Tomography, Emission-Computed; Treatment Outcome

Combination chemotherapy with THP, CDDP and 5-FU for squamous cell carcinoma of the head and neck was conducted in 13 institutions in Hyogo Prefecture as a multi-institutional cooperative study. In the initial study (Nov. 1990-Nov. 1993), THP was administered intravenously at 20 mg/m2 on day 1, CDDP at 80 mg/m2 on day 2, and 5-FU at 1,000 mg/body/day in a continuous drip infusion for 120 hours from day 2 to day 6. In the second study (May, 1996-Mar. 1998), THP was administered at 20 mg/m2 on day 1, 5-FU at 10 mg/kg/day from day 1 to day 5, and CDDP at 70 mg/m2 on day 6 in the same way as the initial study. Forty-nine patients (Stage I in 3, Stage II in 12 including 2 recurrent cases, Stage III in 6, Stage IV in 28 including 3 recurrent cases; 1 course chemotherapy in 13 and 2 or more courses in 36) were subjected as complete cases in the initial study, and 36 patients (Stage I in 5 including one recurrent case, Stage II in 11 including 1 recurrent case, Stage III in 9 including 2 recurrent cases, Stage IV in 11 including one recurrent case; 1 course in 18 and 2 or more courses in 18) in the second. The overall response rate was 65.3% (CR in 3 cases) in the initial study and 63.9% (CR in 5 cases) in the second. Primary cases showed a response rate of 65.9% (29/44) in the initial study and 71.0% (22/31) in the second, whereas recurrent cases showed a 60.0% (3/5) response rate in the initial study and a 20.0% (1/5) rate in the second. Treatment-naive patients showed a response rate of 72.7% (24/33) in the initial study and 71.0% (22/31) in the second, whereas previously treated patients showed a 50.0% (8/16) response rate in the initial study and a 20.0% (1/5) rate in the second. Adverse reactions of more than Grade 3 in the initial study were leukopenia in 18.4%, thrombocytopenia in 8.2%, decrease of hemoglobin in 6.1%, loss of hair in 6.1%, anorexia in 36.7%, nausea and vomiting in 26.5%, and diarrhea in 4.1%, whereas those of Grade 3 in the second study were decrease of hemoglobin in 2.8%, anorexia in 22.2% and nausea and vomiting in 8.3%. From these results, it is suggested that the regimen in the second study was more useful than that in the initial study.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Male; Middle Aged; Treatment Outcome

Head and neck squamous carcinoma (HNSCC) is a chemotherapy-sensitive tumour, but this sensitivity is not reflected in an impact on survival. The study of new drugs is therefore indicated. Pirarubicin (4'-O-tetrahydropyranyl-doxorubicin) has a higher preclinical index than doxorubicin, with low cardiotoxicity in animal models.. Twenty-six patients with squamous cell carcinoma of the head and neck and documented progression after or during previous chemotherapy were entered into the study. Two patients were ineligible for evaluation. Pirarubicin was given at a dose of 70 mg/m2 every 3 weeks.. Partial remission was seen in 1 of the 24 evaluable patients. The predominant toxicity was bone marrow depression, with leucopenia in 62% of the patients. One patient died due to a gastrointestinal haemorrhage during a period with WHO grade IV thrombocytopenia.. On the basis of these results, pirarubicin cannot be recommended as second-line treatment in patients with recurrent and metastatic HNSCC. Its possible relevance for first-line treatment cannot be judged from these data.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Treatment Outcome

4'-0-tetrahydropyranyladriamycin (Pirarubicin, Meiji Seika (USA) Inc., New York, NY) may be less toxic than doxorubicin.. A Phase II trial of Pirarubicin was done in 26 patients who had not previously had chemotherapy and who had measurable and incurable head and neck carcinoma. All patients received an intravenous bolus dose of 60 mg/m2 Pirarubicin in the first cycle without any prophylactic antiemetic. The cycles were repeated every 3 weeks. Based on tumor response, nadir counts, or complications of myelosuppression, the doses were escalated or de-escalated by 10 mg/m2, if necessary, in the second cycle to achieve mild leukopenia (3000-4000 leukocytes/microliters).. Leukopenia was mild, moderate (2000-2999 leukocytes/microliters), severe (1000-1999 leukocytes/microliters), and life threatening (less than 1000 leukocytes/microliters) in 13%, 31%, 27%, and 9% of the first two courses, respectively. The median interval to nadir leukopenia was 13 days (range, 7-21 days), with a median of 8 days (range, 5-13 days) to recover to normal. One patient with a leukocyte count of 800/microliters and an absolute granulocyte count (AGC) of 488/microliters died of sepsis 15 days after the first course. All patients had at least one course that resulted in leukopenia. One episode each of mild (100,000-150,000 platelets/microliters) and severe (25,000-49,999 platelets/microliters) thrombocytopenia occurred in the first two courses. Leukocyte, granulocyte, and platelet counts were not done routinely after the second cycle. Six patients who received four or more courses with cumulative doses of 310, 610, 340, 260, 660, and 550 mg/m2 had decrements of 0%, 1%, 7%, 10%, 12%, and 13%, respectively, in radionuclide left ventricular ejection fraction (LVEF). All other toxic effects were mild.. In the 24 patients with disease evaluable for response to Pirarubicin therapy, 1 had a complete response that lasted 5 months and 4 had a partial response of 2, 3, 6, and 8 months. The median survival time in patients with disease that responded to Pirarubicin therapy was 27 months; in patients with disease that did not respond to Pirarubicin therapy, the median survival time was 4 months, and in the total cohort, it was 5 months. Pirarubicin was well tolerated and was an active agent in head and neck squamous cell carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Doxorubicin; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Salvage Therapy; Survival Analysis

Topics: Adult; Aged; Carcinoma, Squamous Cell; Doxorubicin; Drug Evaluation; Female; Head and Neck Neoplasms; Hematologic Diseases; Humans; Male; Middle Aged

Fourteen patients previously treated with surgery, radiotherapy, and/or chemotherapy for primary squamous cell carcinoma of the head and neck were treated with 4'-O-tetrahydropyranyl-Adriamycin (THP-adriamycin) for locally or distantly recurrent disease. The starting dose was 60 mg/m2 by i.v. infusion, with courses repeated every 3 to 4 weeks. A total of 34 courses of treatment were delivered (median, 2; range, 1-6). All patients were evaluable for response and toxicity. There were no responses. Severe (grade 3 or 4) neutropenia occurred in 11 patients. Thrombocytopenia, anemia, and gastrointestinal toxicity were modest, and no hepatic, renal, or cardiac toxicity was observed. The lack of response in association with severe neutropenia and moderate other toxicities using this dose and schedule of THP-Adriamycin should be taken into consideration prior to the pursuit of further study of this compound in a similar patient population.

Topics: Adult; Aged; Carcinoma, Squamous Cell; Doxorubicin; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged

Objectives To investigate the clinical characteristics, survival and prognosis of patients with multiple myeloma (MM) and head extramedullary plasmacytoma (EMP). Methods Forty MM patients were enrolled in the study (18 men, 22 women; median age, 55 years). Results Median overall survival (OS) and progression-free survival (PFS) were 24 (5-78) months and 17 (2-36) months, respectively. The 2-, 3- and 5-year OS rates were 51%, 20% and 7%, respectively. The 2-year PFS was 15%. Median OS and PFS in patients administered velcade were 26 (18-50) and 22.5 (5-78) months, compared with 20 (10-30) and 13.5 (2-36) months in patients without velcade, respectively. Median OS was 23.5 (5-50) months in patients with EMP at MM diagnosis ( n = 25) and 36 (22-78) months in patients with head EMP diagnosed during the disease course ( n = 15). Sixteen MM patients had EMP invasion of the head only and 24 had invasion at multiple sites. Median OS was 25 (22-78) months in patients with EMP of the head only and 22 (5-78) months in patients with EMP invasion at multiple sites. Conclusion MM patients with head EMP show a more aggressive disease course and shorter OS and PFS. The prognosis of these patients is poor, especially in patients with head EMP at MM diagnosis, though combined chemotherapy and radiotherapy may prolong survival.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Bortezomib; Dexamethasone; Disease Progression; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Ifosfamide; Male; Middle Aged; Multiple Myeloma; Plasma Cells; Plasmacytoma; Prognosis; Prospective Studies; Survival Analysis

To study the effects of superselective intraarterial chemotherapy with low-dose CBDCA, Pirarubicin, and concurrent radiotherapy on head and neck cancer, we compared primary cancer response and histopathological effective grades in 66 patients (more than T2) divided into radical and preoperative radiotherapy groups. The radical group (n=33) showed a 75.7% response in primary cancer, i.e. 54.5% complete remission and 21.2% partial remission. The preoperative group (n = 33) showed 39.4% complete remission when the histopathological effective grade was higher, and 57.6% partial remission when the grade was lower. Cancer response was better in the oral cavity, mesopharynx, and hypopharynx than in the parasinus. In the preoperative group, 5-year overall survival was 84.4% when the effective grade was higher, and 29.4% when the grade was lower. Survival differed significantly (P<0.01) between higher and lower grades. Additional postoperative therapy is thus essential in patients with lower grades of histopathological effectiveness.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Combined Modality Therapy; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Radiotherapy Dosage; Remission Induction; Survival Rate

A 17-year-old girl developed refractory rhabdomyosarcoma. An allogeneic peripheral-blood stem-cell transplant was performed after a myeloablative regimen. Although rapid disease progression had resolved transiently, after the start of high-dose chemotherapy, re-progression was apparently observed from day 14. However, delayed tumor regression occurred on day 30, shortly after the reduction of immunosuppressants. She achieved a partial remission. The second tumor regression provides suggestive clinical evidence that graft-versus-tumor effect may occur against rhabdomyosarcoma. Although further investigation is required, allogeneic stem-cell transplantation could provide a new therapeutic option for refractory rhabdomyosarcoma.

Topics: Adolescent; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Dactinomycin; Disease Progression; Doxorubicin; Drug Resistance, Neoplasm; Etoposide; Fatal Outcome; Female; Graft vs Tumor Effect; Head and Neck Neoplasms; Humans; Ifosfamide; Immunosuppressive Agents; Neoplasm Recurrence, Local; Nimustine; Peripheral Blood Stem Cell Transplantation; Rhabdomyosarcoma; Transplantation Conditioning; Vincristine

Eight cases (4 of the maxillary sinus, 3 of the tongue, and one of the oral floor) of resectable advanced head and neck squamous cell carcinoma were treated preoperatively by means of concurrent chemoradiotherapy with combination of pirarubicin (THP), 5-fluorouracil (5-FU), and radiation between March 2001 and April 2002. THP (5 mg/day) was infused into the maxillary or lingual artery through a catheter placed in the superficial temporal artery one hour before radiotherapy on days 1-5 and 8-12. In addition, continuous intravenous instillation of 5-FU (150 mg/m2/day) was performed on days 1-5, 8-12, 15-19, and 22-26 in accordance with the radiotherapy schedule (2 Gy/day). The total doses of THP, 5-FU, and radiation were 50 mg, 3,000 mg/m2 and 40 Gy, respectively. Five out of 8 patients showed a complete response and the remaining 3 a partial response, for a 100% response rate. In particular, all 4 cases of tongue and oral floor carcinoma showed a complete response. All patients were able to undergo this series of therapy as scheduled without any severe adverse effects. We conclude that this concurrent chemoradiotherapy is feasible for preoperative therapy in view of the good locoregional control rate and the negligible adverse effects.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Combined Modality Therapy; Doxorubicin; Fluorouracil; Head and Neck Neoplasms; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Male; Middle Aged; Perioperative Care

Head and neck cancer has hypoxic compartment. The hypoxic cells are resistant to anticancer drugs and thought to be one of the causes of recurrence. We examined effects of anticancer drugs on the hypoxic cells using HEp-2 human laryngeal cell line. Anticancer drugs, CDDP, peplomycin (PEP), 5-FU, THP-adriamycin (THP-ADR), and adriamycin (ADR), were incubated with cells in hypoxic condition (5% CO2 and 95% N2) for 72 hours. Drug effects were measured by proliferation rates (IC50). IC50 of PEP increased 22.89 folds in hypoxic cells. IC50 of CDDP and 5-FU also increased 1.86 and 2.27 folds respectively. However, IC50 of THP-ADR and ADR remained same in the hypoxic cells. It was proved that THP-ADR and ADR were effective for the hypoxic cells. The combination effect with THP-ADR and CDDP or PEP were more than additive against the hypoxic cells. It was suggested that the combination with THP-ADR and CDDP or PEP are effective for head and neck cancer which contains hypoxic cell compartment.

Topics: Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cell Division; Cell Hypoxia; Cisplatin; Doxorubicin; Drug Synergism; Head and Neck Neoplasms; Humans; Peplomycin

The chemosensitivities of 77 samples of human head and neck cancer were examined by in vitro succinate dehydrogenase inhibition (SDI) test. The tumor tissues obtained at biopsy specimens were exposed to doxorubicin (DXR) and pirarubicin (THP). The average decrease of the enzyme activity by THP was significantly greater than that by DXR. In 60 cases of squamous cell carcinomas, the chemosensitivity of poorly differentiated type tended to be higher compared to the well differentiated type. It is suggested from there results that THP is a more effective anticancer drug than DXR against human head and neck cancers. Clinically good responses were obtained in a systemic chemotherapy of such as head and neck adenoid cystic carcinomas by combining THP with other anticancer drugs such as CDDP (or CBDCA) and CPA.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Adenoid Cystic; Carcinoma, Squamous Cell; Doxorubicin; Drug Screening Assays, Antitumor; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged

Topics: Adenocarcinoma; Adult; Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Etoposide; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged

Twelve patients with advanced or relapsed head and neck adenocarcinoma received a combination chemotherapy regimen of either cyclophosphamide (C), tetrahydropyranyl-adriamycin (T), and cis-platinum (P) (CTP) or cyclophosphamide, adriamycin (A), and cis-platinum (CAP). Cyclophosphamide (300 mg/sq m), either etrahydropyranyl-adriamycin (30 mg/sq m) or adriamycin (30 mg/sq m), and cis-platinum (50 mg/sq m) were administered intravenously in a single day. Nine patients received the CTP regimen, and three patients, the CAP regimen. Prior to chemotherapy, five patients had received surgery or radiation therapy, and the other seven patients received no special treatment. A response rate 75% was achieved (9/12); there were 7 complete responses, whose duration was a mean 6.8 months, ranging from 2 to 18 months, and 2 partial responses, whose duration was 2 months. Virtually all patients experienced nausea and vomiting. Alopecia developed in 7 patients; however, the patients with the CTP regimen experienced less alopecia, if any. Leucopenia and anemia of either a slight or moderate degree were observed, but there was no patient for whom it was necessary to discontinue the treatment. Both CTP and CAP regimens appear to be of significant value in controlling head and neck adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Recurrence, Local

We have studied the pharmacokinetics and metabolism of pirarubicin (4'-O-tetrahydropyranyldoxorubicin) in six patients included in an EORTC phase II study. Pirarubicin was injected as an i.v. bolus of 5 min on 3 consecutive days at a dose of 20 mg/m2 per day. Blood samples were collected at regular times after each injection. Urine was collected over 12 h periods for 3 days and then over 24 h periods. Pirarubicin and metabolites were extracted on Sep-pak cartridges, and analyzed by HPLC with fluorometric detection. Unchanged pirarubicin followed three similar plasma concentration curves, which could be fitted by a two-compartment model with successive half-lives of 22.0 min and 12.7 h. Total plasma clearance of the drug was 90 l/h/m2 and total volume of distribution 1380 l/m2. Doxorubicin was the main metabolite in plasma after an injection of pirarubicin; its concentration was lower than that of pirarubicin but progressively increased from day to day and exceeded the level of pirarubicin 8 h after the 3rd injection of the drug until the end of the blood sampling. Pirarubicinol and doxorubicinol were also metabolites of pirarubicin in plasma; pirarubicinol followed similar plasma concentration curves during the 3 days of treatment whereas doxorubicinol progressively increased from day to day. Total urinary excretion represented about 6% of the dose injected. The same metabolites as in plasma were found in urine. Whereas the total amount of pirarubicin and pirarubicinol was the same in urine during the 24 h after each injection, the amounts of doxorubicin and doxorubicinol excreted increased from day to day, so that doxorubicin became progressively the main compound in urine after the end of the treatment. The progressive accumulation of pirarubicin metabolites (doxorubicin and doxorubicinol) after the repetitive injections of pirarubicin are probably due to the protracted half-lives of these compounds as compared to that of pirarubicin.

Topics: Adult; Aged; Chromatography, High Pressure Liquid; Doxorubicin; Drug Evaluation; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasms; Ovarian Neoplasms; Uterine Neoplasms

A phase II study of a new anthracycline, (2"R)-4'-O-tetrahydropyranyladriamycin (THP), was conducted in 110 patients with various head and neck cancers in a multi-institutional cooperative study. The response rate was 20.3% (PR 12) in an intravenously injected group and 52.3% (CR 8, PR 15) in an intraarterially injected group. In the former cases, the response rate according to primary sites was 19.2 to 27.3% for the maxilla, pharynx, oral cavity and larynx. In the latter cases, it was 40.9 to 64.3% for the maxilla, pharynx and oral cavity, and 100% for the external auditory meatus (CR 1, PR 1). According to histology, the response rate was 37.5 % in squamous cell carcinoma. Partial response was observed in two cases of undifferentiated carcinoma. The predominant toxicity was myelosuppression. Leukocytopenia (less than 3,000/mm3) was noted in 44 cases (41.9%). Loss of hair and stomatitis were observed in 13 (12.6%) and 12 (11.7%) respectively. However, these were mild and recovered quickly on discontinuation of THP. We concluded that THP therapy was markedly effective for various head and neck cancers.

Topics: Alopecia; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Head and Neck Neoplasms; Humans; Infusions, Intra-Arterial; Infusions, Parenteral; Leukopenia; Stomatitis

One-day CAP therapy utilizing CPM, THP-ADM and CDDP was performed on 33 patients with malignant tumors in the head and neck region which were able to be evaluated. As a result, CR was obtained in 6 patients and PR in 11 patients; thus the overall response rate was 51.5%. The present therapy is worthwhile as a neo-adjuvant chemotherapy and it was effective in patients with relatively severe systemic condition or those with lung metastasis. When the tissues were classified histologically, the present therapy was effective against anaplastic carcinoma and adenocarcinoma. Since agents significantly effective against adenocarcinoma have not been available so far, the present therapy is considered to be a useful method especially for the treatment of adenocarcinoma. Moreover, because irreversible side effects scarcely appeared and because the period for 1 course of treatment is short enough, the present therapy is considered to be a method with little burden on patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Cisplatin; Cyclophosphamide; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged

A new anthracycline antibiotic agent, THP-adriamycin (THP-ADM) was administered to patients with malignant head and neck tumors. Among them, intraarterially injected cases achieved excellent primary effects; 3 CR, 4 PR and 2 NC out of 9 cases. Patients received THP-ADM 10 mg/body every other day, to a total of 100 mg. In order to elucidate the factors responsible for this result, the concentration level of THP-ADM in plasma, blood cells and in tumor tissue was measured by high-performance liquid chromatography at various time intervals. Changes in concentration of THP-ADM were similar in both intraarterial and intravenous cases. Among these, the concentration levels in blood cells were always higher than in the plasma and were reduced rapidly with the passage of time; about hour 1 after administration, THP-ADM levels diminished considerably, especially in the plasma. On the other hand, in tumor tissue, the concentration level was exceedingly high at 1 hour after injection, and was still high-24 hours later. In intraarterial cases, these levels were about seventy times higher than in intravenous cases at 1 hour after injection. From these observations, the authors found a very good correlation between the tissue concentration level and the clinical effects obtained.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Squamous Cell; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Injections, Intra-Arterial; Injections, Intravenous; Male; Middle Aged

Primary effects and side-effects of a new anthracycline antineoplastic agent, THP-adriamycin (THP-ADM), were examined in 20 patients with malignant head and neck tumors. According to a classification by tumor sites, there were 6 cases of oropharynx, 6 of nose and sinuses, 3 of tongue, 2 of floor of mouth, 2 of neck and 1 of external auditory meatus. According to the tissue classification, there were 11 cases of squamous cell ca., 6 cases of malignant lymphoma, each one case of anaplastic ca., carcino sarcoma and adeno cystic ca. There were 16 previously untreated cases and 4 pretreated cases. Twelve cases received THP-ADM by intraarterial injection and 8 cases by the same dose. 10 to 20 mg/body 3 times a week, in a total of 40 to 100 mg. 2 CR, 5 PR, 3 MR and 4 NC in 14 cases with carcinoma, and 2 CR, 3 PR and 1 MR in 6 cases with malignant lymphoma were obtained. Among 12 cases receiving intraarterial injection, 3 CR and 5 PR were obtained. The decrease of WBC counts below 3000/mm3 after THP-ADM administration was observed in 9 cases. Side effect of THP-ADM appeared to be less severe than that of Adriamycin.

Topics: Adolescent; Aged; Doxorubicin; Female; Head and Neck Neoplasms; Humans; Injections, Intra-Arterial; Male; Middle Aged