RESUMEN
PURPOSE: This phase I study was performed to assess the feasibility of the combination of docetaxel and cisplatin and to determine the maximum-tolerated dose (MTD) and the side effects with an emphasis on sequence-dependent side effects. MATERIALS AND METHODS: Patients who were not pretreated with taxanes or cisplatin derivatives and who had received no more than one prior combination chemotherapy regimen or two single-agent regimens were entered. Treatment consisted of docetaxel given as a 1-hour infusion followed by cisplatin as a 3-hour infusion (schedule A), or cisplatin followed by docetaxel (schedule B). Docetaxel doses ranged from 55 to 100 mg/m2 and cisplatin doses from 50 to 100 mg/m2. RESULTS: Leukocytopenia and granulocytopenia were common (overall, 90%; grade 3 or 4, 87%), short-lasting, and docetaxel dose-dependent. Infections and neutropenic fever occurred in 10% and 4.5% of courses, respectively. Nonhematologic toxicities were mild to moderate and included alopecia, nausea, vomiting, diarrhea, mucositis, neurotoxicity, fluid retention, and skin and nail toxicity. There were no significant differences in pharmacokinetic parameters between schedules A and B. Tumor responses included one complete response (CR) and nine partial responses (PRs). CONCLUSION: The dose levels docetaxel 100 mg/m2 plus cisplatin 75 mg/m2 and docetaxel 85 mg/m2 plus cisplatin 100 mg/m2 appeared to be manageable. At these dose levels, the median relative dose-intensity was high and 81% and 88% of all cycles, respectively, could be given at full dose. Schedule A is advocated for further treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias/tratamiento farmacológico , Taxoides , Adulto , Anciano , Agranulocitosis/inducido químicamente , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Docetaxel , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Leucopenia/inducido químicamente , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/análogos & derivados , Vómitos/inducido químicamenteRESUMEN
Docetaxel is a new semi-synthetic taxoid, which acts as an antimicrotubule agent and is now clinically available. Clinical studies of docetaxel as a single agent and in combination with other cytotoxic drugs reveals favourable response rates in a number of solid tumor types. Docetaxel appears to have great potential in advanced breast cancer as first or secondline chemotherapy. The dose-limiting toxicity is an early and short-lasting neutropenia. Fluid retention is a cumbersome, sometimes disabling, side-effect. Other side-effects are usually mild and include alopecia, myalgia, mucostitis, neuropathy, hypersensitivity reaction, nail changes and cutaneous reactions.
Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Animales , Antineoplásicos Fitogénicos/farmacocinética , Antineoplásicos Fitogénicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Ensayos Clínicos como Asunto , Docetaxel , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Humanos , Dosificación Letal Mediana , Neoplasias Pulmonares/tratamiento farmacológico , Microtúbulos/efectos de los fármacos , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/farmacocinética , Paclitaxel/farmacología , Paclitaxel/uso terapéutico , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
OBJECTIVES: To determine the response rate and factors correlated with response of oligodendroglial tumors to procarbazine, lomustine (CCNU), and vincristine (PCV) chemotherapy. DESIGN: Retrospective, observational multicenter study. METHODS: Patients treated with PCV or intensified PCV chemotherapy for a recurrent oligodendroglial tumor after surgery and radiation therapy with measurable disease were retrospectively evaluated for response. A 50% reduction in cross-sectional enhancing tumor area was considered a partial response. Stabilized or responding patients received six cycles of PCV unless unacceptable toxicity occurred. RESULTS: Fifty-two patients were included; median time to progression (MTP) for the entire group was 10 months. In 17% of patients a complete response (MTP, 25 months) was obtained, and in 46% a partial response (MTP, 12 months) was obtained. Median overall survival was 20 months. Although treatment was discontinued for toxicity in seven patients, it was generally well tolerated. The intensified PCV regimen was more toxic. Patients initially presenting with seizures and patients with tumor necrosis in histologic specimens had a better response rate in contrast to patients who had their first relapse within 1 year of first treatment (surgery and radiation therapy). CONCLUSIONS: Oligodendroglial tumors are chemosensitive, but most patients will have relapsed after 12 to 16 months. New studies must aim at improving initial treatment and second-line chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Encefálicas/tratamiento farmacológico , Oligodendroglioma/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos Fitogénicos/administración & dosificación , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Femenino , Humanos , Lomustina/administración & dosificación , Imagen por Resonancia Magnética , Masculino , Neoplasias Meníngeas/secundario , Persona de Mediana Edad , Oligodendroglioma/diagnóstico , Oligodendroglioma/patología , Procarbazina/administración & dosificación , Pronóstico , Recurrencia , Estudios Retrospectivos , Vincristina/administración & dosificaciónRESUMEN
Hexadecylphosphocholine (HePC) is a new alkyl phospholipid that has been shown to have antitumour activity in vitro and in vivo. In vivo studies have shown absence of bone marrow toxicity at therapeutic doses. In addition, at the highest dosage group in rats, an increase in white blood cell counts (WBC) was observed. To study the presence of a similar phenomenon in man, frequent measurements of haematological parameters were performed in a series of phase II studies. 70 patients were treated with daily doses of 100-200 mg of the oral formulation of HePC. WBC and platelet counts were performed weekly. In a subgroup of 23 patients serum levels of haemopoietic growth factors were measured before and during treatment. A significant increase in WBC and platelet counts was seen in 74 and 73% of the patients, respectively. In 4 patients, bone marrow showed normal cellularity, and in 1 patient, bone marrow culture showed normal numbers and sizes of colony forming units. No abnormal levels or trends over time of cytokines were observed. We conclude that oral HePC induces an increase in WBC and platelet counts in the majority of those treated.
Asunto(s)
Antineoplásicos/efectos adversos , Leucocitosis/inducido químicamente , Fosforilcolina/análogos & derivados , Trombocitosis/inducido químicamente , Administración Oral , Adulto , Anciano , Antineoplásicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/tratamiento farmacológico , Femenino , Neoplasias de Cabeza y Cuello/sangre , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Humanos , Recuento de Leucocitos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Fosforilcolina/administración & dosificación , Fosforilcolina/efectos adversos , Recuento de Plaquetas , Estudios Prospectivos , Sarcoma/sangre , Sarcoma/tratamiento farmacológicoRESUMEN
Docetaxel is a new antimicrotubule agent that has been shown to be active against a variety of solid tumors. Ifosfamide is an alkylating drug that has demonstrated activity against non-small cell lung cancer, testicular cancer, breast cancer, and soft tissue sarcoma. This phase I study of the combination of these drugs was performed to assess the feasibility of using the two agents together, to determine the maximum tolerated dose and the side effects, and to propose a safe schedule for further phase II studies. Thirty-four patients with histologically confirmed solid tumors who had not been treated previously with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-hour infusion followed by ifosfamide as a 24-hour infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg/m2 and ifosfamide doses from 2.5 to 5.0 g/m2. Grades 3 and 4 granulocytopenia were observed in 89% of courses and appeared to be of short duration and related to the ifosfamide dose. Febrile neutropenia and sepsis occurred in 17% and 2% of courses, respectively. Severe anemia and thrombocytopenia were uncommon. Nonhematologic toxicities were mild to moderate, and included alopecia, nausea, vomiting, mucositis, diarrhea, sensory neuropathy, skin and nail toxicity, hypersensitivity reactions, and edema. Schedule B appeared to induce more gastrointestinal toxicity than schedule A. One complete response in soft tissue sarcoma and two partial responses, one in cancer of unknown primary and the other in non-small cell lung cancer, were documented. The dose-limiting toxicity for schedule A was neutropenic fever at a dose of 85 mg/m2 docetaxel and 5 g/m2 ifosfamide. The dose-limiting toxicity for schedule B was neutropenic fever at a dose of 75 mg/m2 docetaxel and 4 g/m2 ifosfamide. A dose of 75 mg/m2 docetaxel combined with 5 g/m2 ifosfamide according to schedule A can be recommended for further studies.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias/tratamiento farmacológico , Taxoides , Adulto , Anciano , Docetaxel , Estudios de Factibilidad , Femenino , Humanos , Ifosfamida/administración & dosificación , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/análogos & derivadosRESUMEN
A number of novel anticancer agents have emerged during the past few decades, which show high activity in preclinical tumour models and promising activity in early trials in patients with solid tumours. Most of the agents have novel and unique mechanisms of action, and show activity against a variety of malignancies, including tumours which are notoriously resistant to systemic treatment. Recently, our understanding of the molecular basis of cancer has increased considerably. This is reflected in the development of agents that are directed at well defined molecular targets, such as the mitotic tubulin/microtubuli system (taxoids), nuclear enzymes (topoisomerase I inhibitors) and cell signal transduction pathways (protein kinase C inhibitors). In addition, significant advances have been made in our understanding of mechanisms of toxicity, especially of cisplatin. This has resulted in the development of agents modulating cisplatin toxicity, among which amifostine (WR-2721) is one of the most promising. The outlined emerging drug therapies with novel anticancer agents and treatment modalities will, it is hoped, result in increased response rates of advanced tumours, longer disease-free and total survival and better palliative care.
Asunto(s)
Antineoplásicos/uso terapéutico , Indolquinonas , Neoplasias/tratamiento farmacológico , Amifostina/uso terapéutico , Aziridinas/uso terapéutico , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Humanos , Indoles/uso terapéutico , Compuestos Organoplatinos/uso terapéutico , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Proteína Quinasa C/efectos de los fármacos , Inhibidores de Topoisomerasa I , GemcitabinaRESUMEN
PURPOSE: This study was performed to determine the correlation of CA15.3 and TPS with disease course in patients with metastatic breast cancer. METHODS: Levels of CA15.3 and tissue polypeptide antigen using the M3 monoclonal antibody (TPS) were determined in the serum of 60 patients with metastatic breast cancer. CA15.3 and TPS were measured at two assay times. RESULTS: A change of more than 25% in the serum level of CA15.3 or TPS was highly correlated with tumor response. The association between response and change in marker levels was stronger for CA15.3 (P = 0.0001) than for TPS (P = 0.0005). Distinct mismatches between marker changes and the tumor response were observed for both CA15.3 and TPS. CONCLUSION: CA15.3 and TPS are useful in the determination of response to treatment. Because of observed disagreement, marker changes can only be regarded as indicative of disease course.
Asunto(s)
Neoplasias de la Mama/inmunología , Mucina-1/sangre , Antígeno Polipéptido de Tejido/sangre , Adulto , Anciano , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , PronósticoRESUMEN
PURPOSE: Fluid retention, which includes peripheral edema, ascites, pleural or pericardial effusion, or a combination of these that is sometimes associated with significant weight gain, is one of the most troublesome cumulative side effects of docetaxel. A suggestive observation from the data base available at the manufacturer (Rhone-Poulenc Rorer) was that patients who received venotonic drugs appeared to tolerate more courses of docetaxel. This prompted a comparative study to investigate whether the venotonic drug hydroxyethylrutosiden could reduce or delay docetaxel-related fluid retention. METHODS: A total of 85 patients with metastatic breast cancer who were treated with docetaxel at a dose of 100 mg/m2 with corticoid comedication were allocated to receive either 300 mg hydroxyethylrutosiden given orally four times daily (group A) or no hydroxyethylrutosiden (group B). The end point for analysis was the development of fluid retention of > or = grade 2. RESULTS: Fluid retention of > or = grade 2 was reported in 14 of 42 patients (33%) in group A and in 15 of 43 patients (35%) in group B and occurred after a median of 4 cycles of docetaxel in both groups. Weight gain was similar in groups A and B. CONCLUSION: We conclude that hydroxyethylrutosiden does not reduce or delay the incidence and severity of docetaxel-related fluid retention.
Asunto(s)
Antineoplásicos Fitogénicos/efectos adversos , Hidroxietilrutósido/uso terapéutico , Paclitaxel/análogos & derivados , Taxoides , Desequilibrio Hidroelectrolítico/prevención & control , Adulto , Anciano , Ascitis/prevención & control , Neoplasias de la Mama/tratamiento farmacológico , Docetaxel , Edema/prevención & control , Humanos , Persona de Mediana Edad , Paclitaxel/efectos adversos , Derrame Pericárdico/prevención & control , Derrame Pleural/prevención & controlRESUMEN
Pertuzumab represents the first in a new class of targeted therapeutics known as HER dimerisation inhibitors. We conducted a phase Ib study to determine the maximum-tolerated dose, the dose limiting toxicities (DLT), and pharmacokinetic (PK) interaction of docetaxel when administered in combination with pertuzumab. Initially, two dose levels of docetaxel (60 and 75 mg m(-2)) were explored in combination with a fixed dose of 1050 mg of pertuzumab; then two dose levels of docetaxel (75 and 100 mg m(-2)) were explored in combination following a fixed dose of 420 mg of pertuzumab with a loading dose of 840 mg. Both drugs were administered intravenously every 3 weeks. The latter dose of pertuzumab was allowed after an amendment to the original protocol when phase II data suggesting no difference in toxicity or activity between the 2 doses became available. Two patients out of two treated at docetaxel 75 mg m(-2) in combination with pertuzumab 1050 mg suffered DLT (grade 3 diarrhoea and grade 4 febrile neutropaenia). Two out of five patients treated at docetaxel 100 mg m(-2) in combination with pertuzumab 420 mg with a loading dose of 840 mg suffered DLT (grade 3 fatigue and grade 4 febrile neutropaenia). Stable disease was observed at four cycles in more than half of the patients treated and a confirmed radiological partial response with a >50% decline in PSA in a patient with hormone refractory prostate cancer were observed. There were no pharmacokinetic drug-drug interactions. The recommended phase II dose of this combination was docetaxel 75 mg m(-2) and 420 mg pertuzumab following a loading dose of 840 mg.
Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Antineoplásicos/administración & dosificación , Neoplasias/tratamiento farmacológico , Proteínas Recombinantes/administración & dosificación , Taxoides/administración & dosificación , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/farmacocinética , Anticuerpos Monoclonales Humanizados , Antineoplásicos/efectos adversos , Antineoplásicos/farmacocinética , Estudios de Cohortes , Progresión de la Enfermedad , Docetaxel , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Quimioterapia Combinada , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Receptor ErbB-2/antagonistas & inhibidores , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/farmacocinética , Taxoides/efectos adversos , Taxoides/farmacocinética , Factores de Tiempo , Resultado del TratamientoRESUMEN
Patients with connective tissue disease (CTD) who are prone to developed isolated pulmonary hypertension (PH) are primarily young females with a history of Raynaud's phenomenon associated with an exertional dyspnoea. From the start of the disease, pulmonary function tests show a decreased diffusing capacity for carbon monoxide, while X-ray examination shows no obvious abnormalities such as interstitial fibrosis. All patients show, on electrocardiographic examination, evidence of right axis deviation and right ventricular hypertrophy. It has been suggested that PH is found mostly in patients with systemic scerlosis characterized by the CREST syndrome. The histopathological findings are intimal proliferation, narrowing of the vessel lumen and medial fibrosis. These are not specific for CTD. One would expect more signs of vasculitis. Neither signs of lung fibrosis, nor signs of pulmonary emboli are described.
Asunto(s)
Enfermedades del Tejido Conjuntivo/complicaciones , Hipertensión Pulmonar/etiología , Adulto , Artritis Reumatoide/patología , Cardiomegalia/patología , Enfermedades del Tejido Conjuntivo/patología , Electrocardiografía , Femenino , Humanos , Hipertensión Pulmonar/patología , Lupus Eritematoso Sistémico/patología , Persona de Mediana Edad , Esclerodermia Sistémica/patologíaRESUMEN
Docetaxel, a new semisynthetic taxoid that has demonstrated promising activity as an antineoplastic agent, was administered in combination with cisplatin to 63 patients in a dose-escalating study. As both drugs were known to be potentially neurotoxic, peripheral neurotoxicity was prospectively assessed in detail. Neuropathy was evaluated by clinical sum-score for signs and symptoms and by measurement of the vibration perception threshold (VPT). The severity of neuropathy was graded according to the National Cancer Institute's 'Common Toxicity Criteria'. The docetaxel-cisplatin combination chemotherapy induced a predominantly sensory neuropathy in 29 (53%) out of 55 evaluable patients. At cumulative doses of both cisplatin and docetaxel above 200 mg m(-2), 26 (74%) out of 35 patients developed a neuropathy which was mild in 15, moderate in ten and severe in one patient. Significant correlations were present between both the cumulative dose of docetaxel and cisplatin and the post-treatment sum-score of neuropathy (P < 0.01) as well as the post-treatment VPT (P < 0.01). The neurotoxic effects of this combination were more severe than either cisplatin or docetaxel as single agent at similar doses.
Asunto(s)
Antineoplásicos Fitogénicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/efectos adversos , Neoplasias/tratamiento farmacológico , Enfermedades del Sistema Nervioso/inducido químicamente , Paclitaxel/análogos & derivados , Taxoides , Adolescente , Adulto , Anciano , Antineoplásicos Fitogénicos/administración & dosificación , Cisplatino/administración & dosificación , Docetaxel , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Parestesia/inducido químicamenteRESUMEN
Capecitabine and docetaxel are both active against a variety of solid tumours, while their toxicity profiles only partly overlap. This phase I study was performed to determine the maximum tolerated dose (MTD) and side-effects of the combination, and to establish whether there is any pharmacokinetic interaction between the two compounds. Thirty-three patients were treated with capecitabine administered orally twice daily on days 1-14, and docetaxel given as a 1 h intravenous infusion on day 1. Treatment was repeated every 3 weeks. The dose of capecitabine ranged from 825 to 1250 mg m(-2) twice a day and of docetaxel from 75 to 100 mg m(-2). The dose-limiting toxicity (DLT) was asthenia grade 2-3 at a dose of 1000 mg m(-2) bid of capecitabine combined with docetaxel 100 mg m(-2). Neutropenia grade 3-4 was common (68% of courses), but complicated by fever in only 2.4% of courses. Other non-haematological toxicities were mild to moderate. There was no pharmacokinetic interaction between the two drugs. Tumour responses included two complete responses and three partial responses. Capecitabine 825 mg m(-2) twice a day plus docetaxel 100 mg m(-2) was tolerable, as was capecitabine 1250 mg m(-2) twice a day plus docetaxel 75 mg m(-2).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias/tratamiento farmacológico , Taxoides , Adulto , Anciano , Alopecia/inducido químicamente , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Astenia/inducido químicamente , Biotransformación , Capecitabina , Hidrolasas de Éster Carboxílico/metabolismo , Desaminación , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Dexametasona/administración & dosificación , Docetaxel , Esquema de Medicación , Femenino , Fiebre/etiología , Fluorouracilo/metabolismo , Enfermedades Gastrointestinales/inducido químicamente , Humanos , Infusiones Intravenosas , Hígado/enzimología , Masculino , Dosis Máxima Tolerada , Metilprednisolona/administración & dosificación , Persona de Mediana Edad , Neoplasias/patología , Neutropenia/inducido químicamente , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/análogos & derivados , Paclitaxel/farmacocinética , Paroniquia/inducido químicamente , Profármacos/administración & dosificación , Profármacos/efectos adversos , Profármacos/farmacocinética , Inducción de Remisión , Resultado del TratamientoRESUMEN
Docetaxel is a new antimicrotubule agent that induces a predominantly sensory neuropathy that is mild in most patients. This prospective study was performed to determine if corticosteroid co-medication reduces the incidence and severity of docetaxel-induced neuropathy. Two groups of patients treated with docetaxel in subsequent cohorts were prospectively analyzed for neurotoxicity. Group A consisted of 38 patients with a variety of solid tumors, who were treated in studies before corticosteroid co-medication was recommended, while 49 female patients in group B with metastatic breast cancer were treated after co-medication with corticosteroids was introduced as a routine. Neuropathy was evaluated by a clinical sum-score for symptoms and signs, and by measurement of the vibration perception threshold (VPT). The severity of neuropathy was graded according to NCI Common Toxicity Criteria. In 42% of patients of group A and in 65% of patients of group B a mainly mild neuropathy was documented. There was no statistically significant difference in neurotoxicity between group A and B. The cumulative dose of docetaxel showed a significant correlation with post-treatment scores of VPT, sensory sum-score, grade of paresthesias, and grade of neurosensory and neuromotor toxicity. Corticosteroid co-medication does not reduce the development of docetaxel-related neuropathy.
Asunto(s)
Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/uso terapéutico , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Neoplasias/tratamiento farmacológico , Enfermedades del Sistema Nervioso/inducido químicamente , Enfermedades del Sistema Nervioso/prevención & control , Paclitaxel/análogos & derivados , Taxoides , Adulto , Anciano , Neoplasias de la Mama/tratamiento farmacológico , Docetaxel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Estudios ProspectivosRESUMEN
Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias/tratamiento farmacológico , Taxoides , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Docetaxel , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Neutropenia/inducido químicamente , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/análogos & derivados , Vómitos/inducido químicamenteRESUMEN
This phase I study was performed to assess the feasibility of combining cisplatin/etoposide (VP-16) with the arotinoid Ro 40-8757 and to determine the dose-limiting toxicity (DLT) of Ro 40-8757 in this combination. Patients with non-small cell lung cancer were eligible. Treatment consisted of Ro 40-8757 p.o. day 1-21, cisplatin 100 mg/m2 i.v. on day 2 and VP-16 100 mg/m2 i.v. on day 2-4, repeated every 3 weeks. Eighteen patients were evaluable for toxicity and response. The doses of Ro 40-8757 ranged from 84 mg/m2 once daily to 42 mg/m2 thrice daily (tid). DLT consisting of delayed nausea/vomiting was reached at 42 mg/m2 tid. Consequently, the maximum tolerated dose was set at one dose level below the DLT, i.e. 28 mg/m2 tid. Skin toxicity occurred but was well manageable. Pharmacological analyses showed a small increase in the volume of distribution of cisplatin and VP-16 between the first and third course. However, no relationship with side effects was found. A response was achieved in 50% of patients. The combination of cisplatin/VP-16 with Ro 40-8757 appears to be feasible at a dose schedule of 28 mg/m2 tid. The response rate was at the upper rate of what can be expected with cisplatin and VP-16.