RESUMO
PURPOSE: The purpose of this study was to evaluate the clinical efficacy and safety of docetaxel in patients with metastatic breast cancer (MBC) resistant to doxorubicin or mitoxantrone. PATIENTS AND METHODS: Docetaxel 100 mg/m2 was administered as a 1-hour intravenous (IV) infusion every 3 weeks to 42 patients registered at four centers. Patients must have received at least one but no more than two prior chemotherapy regimens for MBC (in addition to any prior adjuvant therapy). One of the regimens for metastatic breast cancer must have included an anthracycline or anthracenedione and the cancer must have progressed on that regimen. RESULTS: Objective responses were seen in 20 of 35 assessable patients (three complete responses [CRs] and 17 partial responses [PRs]), for an objective response rate of 57% (95% confidence interval [CI], 39% to 74%) and in 21 of 42 registered patients (50% response rate [RR]; 95% CI, 34% to 66%) entered onto the trial. The median response duration was 28 weeks. The most common toxicity in this study was grade 4 neutropenia, which occurred in 95% of patients. Other clinically significant nonhematologic side effects included stomatitis, skin reactions, neurosensory changes, asthenia, and fluid retention. Patients who received dexamethasone premedication had a later onset of fluid retention than those who did not receive dexamethasone (onset at a median cumulative docetaxel dose of 503 mg/m2 and 291 mg/m2, respectively). CONCLUSION: Docetaxel at this dose and schedule has a high level of antitumor activity in patients with treatment-refractory advanced breast cancer, and appears to be one of the most active agents for the treatment of this patient population.
Assuntos
Antraciclinas/farmacologia , Antraquinonas/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Docetaxel , Doxorrubicina/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade , Mitoxantrona/uso terapêutico , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêuticoRESUMO
PURPOSE: To determine the efficacy (objective response rate and duration of response and survival) and toxicity of docetaxel in patients with strictly defined anthracycline-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: Thirty-five patients with bidimensionally measurable MBC who had progressive disease while receiving anthracycline-containing chemotherapy were registered onto the phase II trial. Docetaxel was administered at a dose of 100 mg/m2 over 1 hour every 21 days. RESULTS: Thirty-four patients were assessable for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a partial response. The median times to disease progression and survival duration were 7.5 and 13.5 months, respectively, for responding patients. The median overall survival duration was 9 months. Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia with less than 500 cells/microL developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208 cycles and in 18 (51%) of 35 patients, including one treatment-related death. Fluid retention was seen in 15 (43%) of 35 patients, including pleural effusions in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed in 16%, 58%, and 37% of cycles, respectively. CONCLUSION: Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC. High objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel is associated with severe but reversible neutropenia, asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/efeitos adversos , Docetaxel , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêuticoRESUMO
Our experience with the combination of dacarbazine, carmustine, cisplatin with and without tamoxifen is reported. In our initial study, with all 4 drugs, we had an overall response rate of 50% with a complete response rate of 15%. Due to a high incidence of deep venous thrombosis and the lack of effectiveness of tamoxifen as a single agent, we deleted tamoxifen from the regimen and treated another 20 patients. Surprisingly, the response rate decreased to 10%. We then re-incorporated tamoxifen into the regimen and treated 25 additional patients. In this third group of patients we experienced an objective response rate of 52% with a complete response rate of 8%. Overall, 65 patients have been treated: 45 with and 20 without tamoxifen. Twenty-three (51%) patients treated with tamoxifen have responded, with 5 (11%) patients achieving a complete response. Only 2 (10%) patients treated without tamoxifen have responded. Despite the improvement in the response rate, a corresponding increase in survival has not been seen. Patients treated with tamoxifen had a mean survival of 10.8 (SD 13.6) months compared with a mean survival of 9.8 (SD 7.3) months for those treated without tamoxifen. The absence of survival advantage for the tamoxifen-treated patients may be due to early failure in the central nervous system. In 48% of the responding tamoxifen-treated patients, the first site of failure was the central nervous system, while systemic disease was still responding.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Tamoxifeno/administração & dosagem , Adulto , Idoso , Cisplatino/administração & dosagem , Humanos , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
The combination of dacarbazine (DTIC, 220 mg/m2) and cisplatin (DDP, 25 mg/m2) IV daily for 3 days every 3 weeks, carmustine (BCNU, 150 mg/m2) IV every 6 weeks, and tamoxifen (TAM, 10 mg orally twice daily) produced a 50% objective response rate in patients with metastatic melanoma. Associated with this treatment, there was a high incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE). In an effort to reduce this toxicity, this regimen minus TAM was studied, and the results are reported. Twenty of twenty patients are evaluable for response and toxicity. There was one complete response (CR) lasting 5+ months and one partial response (PR) lasting 4+ months for an overall response rate of 10% (95% confidence limits, 1.23% to 31.70%). Two patients exhibited a mixed response and three patients developed disease stabilization lasting 4 to 10 months. Toxicity was similar to the original study except that no patients developed DVT or PE. This statistically significant (Fisher's exact test [two-tail] P = 0.008) decrease in the response rate by comparison with that achieved with the TAM-containing regimen may signal an essential role of TAM in this regimen. TAM may be acting in synergy with cisplatin through its calcium channel-blocking properties. TAM should be included as described in the initial reports, and the patients should be carefully observed for vascular complications.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Dacarbazina/administração & dosagem , Feminino , Doenças Hematológicas/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/induzido quimicamente , Tamoxifeno/efeitos adversos , Tromboflebite/induzido quimicamenteRESUMO
This chapter has served to highlight many of the important medical problems seen in the oncology patient. These problems stem from the effects of malignancy itself as well as from treatment. An overall understanding of these disorders and their management is essential to the proper preoperative evaluation of the cancer patient.
Assuntos
Neoplasias/cirurgia , Cuidados Pré-Operatórios , Humanos , Neoplasias/complicações , Neoplasias/diagnósticoRESUMO
Twenty-three patients with metastatic melanoma were treated with combination therapy consisting of dacarbazine (220 mg/m2) and cisplatin (25 mg/m2) iv daily for 3 days every 3 weeks, carmustine (150 mg/m2) iv every 6 weeks, and tamoxifen (10 mg) orally twice daily. In 20 evaluable patients, there were no complete responses and ten partial responses. The median remission duration has not yet been reached but exceeds 7 months. Treatment was relatively well tolerated. However, six patients developed deep venous thrombosis, and four of these six suffered pulmonary emboli. Our data support a previous study and suggest that this combination warrants comparison with the active single components in a randomized prospective trial.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carmustina/administração & dosagem , Cisplatino/administração & dosagem , Dacarbazina/administração & dosagem , Feminino , Humanos , Nefropatias/induzido quimicamente , Leucopenia/induzido quimicamente , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Embolia Pulmonar/induzido quimicamente , Tamoxifeno/administração & dosagem , Trombocitopenia/induzido quimicamente , Tromboembolia/induzido quimicamente , Vômito/induzido quimicamenteRESUMO
A retrospective study of the medical records of 102 patients with Stage II malignant melanoma was conducted to determine the frequency of occult residual melanoma after excision of a clinically positive regional lymph node. Twenty-one patients met the study criteria for evaluation. Fifteen of 22 dissections were positive for melanoma (68.1%). These results support definitive regional lymph node dissection if the results of excisional biopsy are abnormal. No conclusions can be drawn from these data regarding the survival advantage of therapeutic regional lymph node dissection.
Assuntos
Excisão de Linfonodo , Linfonodos/patologia , Melanoma/diagnóstico , Humanos , Metástase Linfática , Estudos RetrospectivosAssuntos
Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Piperazinas/uso terapêutico , Razoxano/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A patient with malignant melanoma of the choroid and ciliary body had a primary cutaneous melanoma and the B-K mole syndrome phenotype. Because of this newly described association, all patients with the B-K mole syndrome (phenotype) should have a complete ocular examination to discover if there is any evidence of ocular melanoma. Likewise, all patients with ocular melanoma should have a thorough dermatologic examination to determine evidence of cutaneous melanoma and the B-K mole syndrome (phenotype).
Assuntos
Neoplasias da Coroide/genética , Melanoma/genética , Neoplasias Primárias Múltiplas/genética , Nevo Pigmentado/genética , Neoplasias Cutâneas/genética , Neoplasias da Coroide/cirurgia , Humanos , Masculino , Melanoma/cirurgia , Pessoa de Meia-Idade , Fenótipo , Neoplasias Cutâneas/cirurgia , SíndromeRESUMO
Nine established human melanoma tissue-cultured cell lines heterotransplanted in C57BL/6 "nude" mice were exposed to each of 4 chemotherapeutic agents of known clinical activity against human melanoma. Two of the therapeutic agents, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-(3,3-dimethyl-1-triazino) imidazole-4-carboxamide (DTIC), are known to be active against human melanoma; the other two, adriamycin and 5-azacytidine, are known to be inactive. Sterile saline served as a control agent. In 2 cell line heterotransplants, the control tumor spontaneously regressed. Of the 7 cell lines that remained for evaluation, 4 were sensitive to DTIC, 1 was sensitive to BCNU, and none was sensitive to adriamycin or 5-azacytidine. These data indicate that the nude mouse-human tumor model may be a predictive secondary screen for cancer chemotherapeutic agents.
Assuntos
Antineoplásicos/uso terapêutico , Avaliação Pré-Clínica de Medicamentos/métodos , Melanoma/tratamento farmacológico , Animais , Azacitidina/uso terapêutico , Carmustina/uso terapêutico , Dacarbazina/uso terapêutico , Doxorrubicina/uso terapêutico , Resistência a Medicamentos , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Neoplasias Experimentais/tratamento farmacológicoAssuntos
Formação de Anticorpos/efeitos dos fármacos , Melanoma/tratamento farmacológico , Compostos de Nitrosoureia/efeitos adversos , Semustina/efeitos adversos , Adulto , Idoso , Antígenos/administração & dosagem , Dinitroclorobenzeno/imunologia , Escherichia coli/imunologia , Feminino , Hemocianinas/imunologia , Humanos , Hipersensibilidade Tardia , Leucopenia/induzido quimicamente , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Toxoide Tetânico/imunologia , Fatores de TempoAssuntos
Antineoplásicos/uso terapêutico , Linfócitos/imunologia , Melanoma/imunologia , Adulto , Idoso , Vacina BCG/uso terapêutico , Linhagem Celular , Citotoxicidade Imunológica , Quimioterapia Combinada , Feminino , Humanos , Imunoterapia , Masculino , Melanoma/tratamento farmacológico , Melanoma/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Semustina/uso terapêutico , Vincristina/uso terapêuticoRESUMO
ICRF-159, at a dose of 300 mg/m2, was given orally every 8 hours for nine doses every 21 days to 40 patients with metastatic breast cancer refractory to hormonal therapy and cyclophosphamide, methotrexate, 5-fluorouracil, and adriamycin chemotherapy. Two patients with soft tissue disease had short-lived partial responses. The hematologic toxicity was severe. Three patients required rbc transfusions. Four patients became septic at the nadir of leukopenia; two of these patients died while leukopenic. Two patients had platelet counts less than 25,000/mm3. All patients who were nonevaluable or who had life-threatening or lethal toxicity were nonambulatory. Since the 19 nonambulatory patients had a median survival of only 1.25 months as compared to 7 months in ambulatory patients, it is recommended that future phase II trials in chemotherapy-refractory breast cancer be limited to ambulatory patients. Although ICRF-159 has minimal antineoplastic effects, it is not recommended for further investigations in metastatic breast cancer, even at more hematologically tolerable doses of 250 mg/m2 every 8 hours for nine doses.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Piperazinas/uso terapêutico , Razoxano/uso terapêutico , Contagem de Células Sanguíneas , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Feminino , Humanos , Metástase Neoplásica , Razoxano/efeitos adversos , Fatores de TempoRESUMO
Twenty-five patients with measurable metastatic melanoma refractory to DTIC and a nitrosourea were treated with dibromodulcitol (DBD). DBD was administered orally at bedtime at a dose of 100 mg/m2/day until hematologic toxicity (a greater than or equal to 50% decrease in the wbc or platelet count) was induced. Five patients experienced clinically useful objective remissions; responding lesions included both soft tissue metastases and visceral metastatic disease. It is concluded that DBD is useful in the treatment of patients with metastatic melanoma and thus joins DTIC and the nitrosoureas as single agents which are active against this malignancy.
Assuntos
Dacarbazina/farmacologia , Melanoma/tratamento farmacológico , Mitolactol/uso terapêutico , Compostos de Nitrosoureia/farmacologia , Triazenos/farmacologia , Adulto , Idoso , Medula Óssea/efeitos dos fármacos , Avaliação de Medicamentos , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitolactol/administração & dosagem , Mitolactol/toxicidade , Metástase Neoplásica , Remissão EspontâneaAssuntos
Melanoma/tratamento farmacológico , Podofilotoxina/análogos & derivados , Teniposídeo/uso terapêutico , Adolescente , Adulto , Idoso , Ensaios Clínicos como Assunto , Avaliação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Teniposídeo/administração & dosagem , Teniposídeo/efeitos adversosRESUMO
Thirty (30) patients with advanced metastatic malignant melanoma refractory to DTIC (NSC-45388) and a nitrosourea were treated with 5-azacytidine (NSC-102816). 5-Azacytidine was administered subcutaneously at a dosage of 100 mg/m2/day for 10 days. Twenty-six (26) patients were evaluable for toxicity and response. Major organ toxicities were hematologic, gastrointestinal, and cutaneous; no antitumor activity was noted.
Assuntos
Azacitidina/uso terapêutico , Melanoma/tratamento farmacológico , Azacitidina/administração & dosagem , Azacitidina/efeitos adversos , Medula Óssea/efeitos dos fármacos , Dacarbazina/uso terapêutico , Avaliação de Medicamentos , Resistência a Medicamentos , Feminino , Humanos , Injeções Subcutâneas , Masculino , Metástase Neoplásica/tratamento farmacológico , Vômito/induzido quimicamenteAssuntos
Piperazinas/uso terapêutico , Razoxano/uso terapêutico , Alopecia/induzido quimicamente , Animais , Neoplasias do Colo/tratamento farmacológico , Humanos , Leucopenia/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Linfoma/tratamento farmacológico , Melanoma/tratamento farmacológico , Camundongos , Náusea/induzido quimicamente , Neoplasias Experimentais/tratamento farmacológico , Razoxano/efeitos adversos , Razoxano/metabolismo , Neoplasias Retais/tratamento farmacológico , Sarcoma/tratamento farmacológicoRESUMO
Eighteen patients with surgically incurable metastatic malignant melanoma were treated with a mixture of irradiated (15,000 rads) autologous tumors cells (1-2 X 10(8)) and BCG (Glaxo, 2-4.5 X 10(6) organisms), which was injected intradermally (in five divided doses) every 2 weeks (X5). Four of 18 (22%) evaluable patients achieved objective remissions. It is concluded that this treatment regimen does not have general clinical application because the remissions were infrequent, of shor duration (median, 3 months) and occurred only in patients with minimal, nonvisceral tumor burdens.