RESUMO
We have conducted a Phase I and initial clinical pharmacological evaluation of 4'-deoxydoxorubicin (4'-DXDX), administering the drug i.v. on an every 21-day schedule to 60 patients with advanced cancer. Patients were treated at six dosage levels ranging from 10 to 35 mg/sq m. Leukopenia was the dose-limiting toxic effect, and no cardiac, renal, or hepatic toxicity was observed; stomatitis was not seen; and there were no drug-related deaths. Significant alopecia was rare at doses less than 35 mg/sq m, mild nausea and vomiting occurred in one-third of patients at myelosuppressive doses; 12 patients had a transient local urticarial reaction. In the 30 patients with measurable disease, two partial remissions were seen, lasting 5 months in a patient with a nasopharyngeal adenocarcinoma, and 7 months in a patient with endometrial adenocarcinoma. The recommended dose of 4'-DXDX for Phase II studies is 30 mg/sq m in good-risk patients and 25 mg/sq m in moderate-risk or heavily pretreated patients. Pharmacokinetic studies were carried out in ten patients, four of whom received 4'-DXDX at a dose of 10 mg/sq m and six at 30 mg/sq m. Disappearance of 4'-DXDX from plasma was triphasic with a rapid initial phase clearance showing a t1/2 alpha of 1 to 2 min and a prolonged terminal phase with a median t1/2 gamma in excess of 90 h in patients receiving 30 mg/sq m.
Assuntos
Antineoplásicos/uso terapêutico , Doxorrubicina/análogos & derivados , Neoplasias/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/metabolismo , Doxorrubicina/efeitos adversos , Doxorrubicina/metabolismo , Doxorrubicina/uso terapêutico , Avaliação de Medicamentos , Feminino , Coração/efeitos dos fármacos , Humanos , Cinética , Masculino , Pessoa de Meia-IdadeRESUMO
Thirty patients with advanced seminoma were treated with VAB-6. Eighteen patients were previously untreated, eight had relapsed after radiation therapy, and four had persistent disease following chemotherapy and radiation therapy. Two patients had received prior high-dose cisplatin. Twenty-four (86%) of 28 evaluable patients achieved a complete remission. Four patients had relapsed. The median disease-free follow-up of patients achieving complete remission was 32+ months. VAB-6 is effective treatment for patients with advanced seminoma, and chemotherapy is recommended as the initial therapy in all patients with stage II seminoma with disease larger than 5 cm, extragonadal seminoma, and stage III seminoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Disgerminoma/tratamento farmacológico , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bleomicina/administração & dosagem , Bleomicina/efeitos adversos , Clorambucila/administração & dosagem , Clorambucila/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dactinomicina/administração & dosagem , Dactinomicina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Humanos , Masculino , Vimblastina/administração & dosagem , Vimblastina/efeitos adversosRESUMO
A phase II trial of gallium nitrate (250-300 mg/m2/day for 7 consecutive days) was conducted in patients with metastatic melanoma. Therapy was well-tolerated, but only one of 31 evaluable patients experienced a partial regression. Further evaluation of gallium nitrate at this dose and schedule is not warranted in patients with malignant melanoma.