RESUMO
60 patients with metastatic breast cancer were entered in a phase II study using folinic acid, 5-fluorouracil bolus and infusion and mitoxantrone with or without cyclophosphamide. 47 had measurable visceral metastases and 13 had exclusively bone metastases. 36 had received previous adjuvant or metastatic treatment (33/36 with anthracycline-based regimens). Overall response rate in visceral metastatic patients was 57.1% [95% confidence interval (CI) 35.4-78.8%]; 45.5% and 70% in previously and non-previously treated patients, respectively; duration of response was 9 and 13 months, respectively. 10 out 13 patients with exclusive bone metastases improved for a median time of 18 months. Median survival was 22 months for the 60 patients; 18 and 31 months for previously and non-previously treated patients, respectively. Cyclophosphamide was scheduled only in the absence of nadir grade 4 neutropenia. However, this toxicity occurred in the first 7 patients. For this reason, we chose to avoid cyclophosphamide in patients over 60 years, or with a performance status of 1-2, or who had received previous chemotherapy. Overall, cyclophosphamide was stopped due to nadir grade 4 neutropenia in 17/24 patients for whom this drug was planned. When mitoxantrone, 5-fluorouracil and folinic acid were used at the doses scheduled, the addition of cyclophosphamide appeared feasible in only about 25% of the patients. Furthermore, survival was identical for patients receiving or not receiving cyclophosphamide. Therefore, cyclophosphamide does not contribute substantially to this regimen. This study confirms the value of folinic acid, 5-fluorouracil and mitoxantrone in metastatic breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Neoplasias Ósseas/secundário , Neoplasias da Mama/mortalidade , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Metástase Neoplásica , Neutropenia/induzido quimicamente , PrognósticoRESUMO
40 patients with advanced ovarian cancer were treated with immediate debulking followed by sequential cisplatin and doxorubicin every 4 weeks, followed by second-look laparotomy (SLL). Six courses were given when residual disease (RD) was under 2 cm. When RD was over 2 cm, three courses were followed by early debulking and six more courses before SLL. Immediate debulking was optimal in 15 patients (38%) and early debulking in an additional 15 (38%). Pathological complete responses (34 evaluable cases) were observed in 14 cases (41%), partial response in 13 (38%), stable disease in 3 (9%) and progression in 5 (15%). Toxicity was mainly haematological. 11 patients with negative SLL and 15 with RD under 2 cm received intraperitoneal cisplatin 200 mg/m2 alone or with cytarabine. Median survival was 45 months: 58 months for RD under 2 cm at initial laparotomy and 31 months for RD over 2 cm. Median survival was 46 months when early debulking was successful. 5 year disease-free survival was only 16%. However, this multimodal treatment offers prolonged survival, especially in patients optimally debulked either at initial laparotomy or at early debulking surgery.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/terapia , Adulto , Idoso , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Injeções Intraperitoneais , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , PrognósticoRESUMO
Oxaliplatin has shown in vivo cytotoxic activity against colorectal cell lines. Preliminary studies suggest potentiation of fluorouracil (5-FU). To assess this issue, we performed a phase II study in pretreated patients with advanced colorectal cancer (CRC) resistant to leucovorin and 5-FU. The regimen (FOLFOX2) consisted of oxaliplatin 100 mg/m2 as a 2-h infusion on day 1; leucovorin 500 mg/m2 as a 2-h infusion, followed by 5-FU 24-h infusion 1.5-2 g/m2 for two consecutive days every 2 weeks. The initial 5-FU dose was 1.5 g/m2 for two cycles and increased to 2 g/m2 in case of no toxicity > grade 2. 46 patients were treated, all with disease progression on leucovorin and 5-FU therapy for metastatic disease, or relapse less than 6 months after the end of adjuvant therapy. One complete response (CR) and 20 partial responses (PRs) were observed for an overall response rate of 46%. 22 patients had prior documented progression while receiving the same schedule of leucovorin and 5-FU as the one used in the FOLFOX2 regimen, and among them, 10 had PRs (45%). From the start of FOLFOX2, median progression-free survival was 7 months and median survival 17 months. WHO toxicity > or = grade 3 per patient was: peripheral neuropathy 9%, nausea 4%, diarrhoea 9%, mucositis 13%, neutropenia 39%, thrombocytopenia 11%, alopecia 9%, and allergy 2%. Overall, 21 patients (46%) experienced grade 3-4 toxicity. This combination of leucovorin, 5-FU and oxaliplatin achieves a high response rate in pretreated patients with CRC resistant to leucovorin and 5-FU. Limiting toxicities are neutropenia and peripheral neuropathy.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/patologia , Neoplasias Retais/patologia , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We studied survival in 36 patients with Stage III/IV ovarian cancer who received intraperitoneal high-dose cisplatin (200 mg/m2) alone or in combination with cytarabine (2 g), after intravenous (i.v.) cisplatin-based chemotherapy followed by second-look laparotomy. Complete responders were scheduled for three courses of IP chemotherapy, and others for six. Eight patients (22%) did not complete treatment (6 catheter failures and 2 renal failures). Peritoneal cytology remained positive in 6 patients (17%). Median overall and progression-free survival after second-look laparotomy were 44 and 37 months, respectively, for 13 complete responders to i.v. chemotherapy; 24 months and 11 months for patients with residual tumors less than 2 cm (17 cases); 15 and 12 months with tumors greater than 2 cm (6 cases). There was a significant difference in overall (p = 0.05) and progression-free (p = 0.001) survival between complete responders to i.v. chemotherapy and patients whose tumor was less than 2 cm. We find no evidence that high-dose cisplatin-based intraperitoneal chemotherapy given after second-look laparotomy will enhance survival in advanced ovarian cancer with zero or minimal residual disease.
Assuntos
Cisplatino/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/efeitos adversos , Terapia Combinada , Citarabina/administração & dosagem , Feminino , Humanos , Infusões Parenterais , Neoplasias Ovarianas/cirurgia , Reoperação , Análise de SobrevidaRESUMO
Eighteen patients with advanced gastric cancer were treated with cisplatin 80 mg/m2 d 1, doxorubicin 30 mg/m2 d 3 and mitomycin-C 12 mg/m2 d 3. One complete and 6 partial responses were observed in 17 evaluable patients (41%, confidence interval 17-65%). Median duration of response was 7 months; median survival was 8 months. One death due to toxicity was observed. This combination of 3 active drugs should not be recommended in cases of gastric cancers.
Assuntos
Cisplatino/uso terapêutico , Doxorrubicina/uso terapêutico , Mitomicina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Estadiamento de Neoplasias , Neoplasias Gástricas/patologiaRESUMO
We report a french experience of subcutaneous administration of interleukin-2 in treatment of patients with metastatic renal cell carcinoma. Thirty-nine patients with metastatic renal cell carcinoma were included in the study. During the 10-week induction period, interleukin-2 was administrated subcutaneously 5 days a week for 8 weeks. The weekly dosage were 90 MIU during weeks 1 and 6; 63 MIU during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with stable disease received maintenance treatment which was discontinued upon the appearance of disease progression or unacceptable toxicity. During the maintenance period, interleukin-2 was administered 5 days a week for 4 weeks followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63 MIU in weeks 2 to 4. After completion of induction treatment, 7 of 39 evaluable patients (18%) had objective responses with 1 complete response. A diminution of dose or interruption of treatment occurred with 7 patients because severe toxicity. Other systemic side effects in the remaining patients were acceptable. Seventeen patients received maintenance treatment. The median follow-up of all the patients included was 21 months. The 1, 2 and 3 years survivals were 64%, 33% and 22% respectively. This multicentric trial confirms the efficacity of subcutaneously-administered interleukin-2 in patients with metastatic renal cell carcinoma in terms of both response rate and survival. Unfortunately, increasing total doses of administrated interleukin-2 does not seem to increase efficacity according to response rate, but is more toxic.
Assuntos
Assistência Ambulatorial , Carcinoma de Células Renais/tratamento farmacológico , Interleucina-2/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Carcinoma de Células Renais/patologia , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Subcutâneas , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas Recombinantes/uso terapêutico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We studied the levamisole toxic effects in adjuvant therapy for colorectal cancer. The therapy toxic effects on 127 patients were statistically more important in the levamisole-treated group compared to patients treated with folinic acid and 5-fluorouracil alone. Randomized studies in progress will demonstrate the real therapeutic value of levamisole.
Assuntos
Adenocarcinoma/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Levamisol/efeitos adversos , Adenocarcinoma/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Colorretais/cirurgia , Terapia Combinada , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Levamisol/uso terapêutico , Estudos RetrospectivosRESUMO
A 58 year-old woman was hospitalized for an hemorrhagic stroke, associated with a consumption's coagulopathy, related to a stage Ic ovarian carcinoma. After surgery and chemotherapy, hemostasic disorders disappeared. The same disorders occurred at tumoral relapse. Relationships between thrombotic or haemorrhagic manifestations and neoplasms are discussed, with emphasis on singularity of such phenomenon in ovarian carcinoma.
Assuntos
Adenocarcinoma/complicações , Hemorragia Cerebral/etiologia , Transtornos Cerebrovasculares/etiologia , Coagulação Intravascular Disseminada/etiologia , Neoplasias Ovarianas/complicações , Adenocarcinoma/fisiopatologia , Hemorragia Cerebral/fisiopatologia , Transtornos Cerebrovasculares/fisiopatologia , Coagulação Intravascular Disseminada/fisiopatologia , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/fisiopatologia , Recidiva , Fatores de TempoRESUMO
Paclitaxel is a new antimitotic derived from yew-tree, used for the treatment of ovarian and breast cancers. The local toxicity of paclitaxel is still poorly known. We report one of the first observations of accidental subcutaneous extravastion of paclitaxel. Local epidermic necrosis was observed and evolution was good with local treatment only. Treatments of such extravasation are discussed.
Assuntos
Toxidermias/etiologia , Extravasamento de Materiais Terapêuticos e Diagnósticos/complicações , Paclitaxel/efeitos adversos , Idoso , Feminino , Humanos , Necrose , Pele/patologiaRESUMO
The main prognostic factor in advanced ovarian cancer is the volume of residual disease after the initial laparotomy. Early debulking surgery after several cycles of chemotherapy, before the emergence of resistant cell lines, could improve the prognosis of patients with bulky residual disease. This study concerns patients with advanced ovarian cancer entered into three prospective trials including IV cisplatin and anthracycline-based chemotherapy, early debulking surgery after three cycles of chemotherapy in case of initial residual disease superior 2 cm and intraperitoneal consolidation chemotherapy. Among 160 patients with stage III or IV, 80 (50%) had at least a residual tumor of more than 2 cm in diameter. Early debulking surgery was effectively performed in 54 patients (67.5%), leaving 39 patients with no residue over 2 cm. Twenty-one patients had no macroscopic residual disease. The median survival of all patients with initial residual disease over 2 cm was 23 months. Patients with no macroscopic residual disease at early debulking surgery had a median survival of 44 months. Early debulking surgery appears useful in advanced ovarian cancer with bulky residual disease. The objective of this operation is to achieve no macroscopic residual lesion.
Assuntos
Carcinoma/terapia , Neoplasias Ovarianas/terapia , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Terapia Combinada , Árvores de Decisões , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Prognóstico , Reoperação , Análise de SobrevidaRESUMO
Second-look laparotomy (SLL) was performed after chemotherapy in 106 patients with epithelial ovarian cancer. Thirteen were stage I and II and 93 stage III and IV. Seventy-eight patients received cisplatin-based regimens. Median follow-up was 60 months. Negative SLL was found in 32 patients who had a 5-year survival rate of 43.4% after SLO. Microscopy residual disease was present in 9 patients whose 5-year survival rate was 25%. Maximum residual tumor of 2 cm or less was found in 13 patients with 5-year survival rate of 30%. Residual tumor larger than 2 cm after secondary cytoreduction was present in 21 patients, their 3-year survival rate was 18.3%. Eighteen patients with bulky residual disease who did not have cytoreduction were all dead within 17 months. Patients with initial residual tumor at first laparotomy less than 2 cm had a near significant advantage in survival rate over patients with residual disease greater than 2 cm and stage IV (p = 0.07). Non-responders to initial chemotherapy had a survival rate similar to that of partial-responders. These findings justify discontinuation of conventional systemic chemotherapy for patients showing residual disease after SLL and secondary tumor removal in case of residual tumor at SLL. Therapeutic trials are needed in advanced ovarian cancer testing initial aggressive surgery or early debulking to avoid bulky residual disease and consolidation therapy in patients who achieved complete pathological response or minimal residual intraperitoneal disease.
Assuntos
Neoplasias Ovarianas/terapia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Laparotomia , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , PrognósticoRESUMO
We studied a series of 42 patients with advanced ovarian cancer who received intraperitoneal chemotherapy post second-look laparotomy. High-dose cisplatin (200 mg/m2) alone or in combination with cytarabine (2 g) achieved 47% response rate. Median overall survival from second-look laparotomy was 44 months with cisplatin (36 cases), 15 months with carboplatin (600 mg/m2, 5 cases) and not reached at 3 yrs with mitoxantrone (25 mg/m2, 8 cases). Median overall and progression-free survival from second-look laparotomy were 44 and 39 months respectively in complete responders (15 cases), 20 months and 9 months where residual tumor less than 2 cm (21 cases), 22 and 12 months where tumor greater than 2 cm (6 cases). There was a significant difference in survival (P = 0.01) and progression-free survival (P = 0.002) between complete responders and patients whose tumor was less than 2 cm. Toxicity was acceptable except for carboplatin with constant grade 4 leukocytes or platelets toxicity. It was not demonstrated that high-dose intraperitoneal chemotherapy given post second-look laparotomy will improve survival in advanced ovarian cancer. Further studies of polychemotherapy or early administration are needed.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carboplatina/administração & dosagem , Cisplatino/administração & dosagem , Citarabina/administração & dosagem , Feminino , Humanos , Infusões Parenterais , Mitoxantrona/administração & dosagem , Neoplasias Ovarianas/mortalidade , Taxa de SobrevidaRESUMO
AIM OF THE STUDY: To determine the characteristics of 51 cases of isolated local regional breast cancer recurrence. METHODS: Retrospective study from 1980 to 1992, survival calculated according to Kaplan-Meier and log-rank test. RESULTS: Twenty-five patients had had a conservative treatment of her primary tumour, 26 had been treated by modified radical mastectomy. Local regional recurrence rate was 9%: 44% of recurrences after lumpectomy and 43% of recurrences after mastectomy occurred within 2 years after the initial treatment. Site of local regional recurrence was chest wall only (16 cases), breast only (15 cases) or axillary or supraclavicular node with or without chest wall or breast involvement (20 cases). The actuarial 5-year survival rate after recurrence is 54%. It depends on the time to recurrence (40% if time to recurrence was less than 2 years, 68% if more than 2 years, p < 0.10), on initial node involvement (36% for N+, 71% for N-, p < 0.15) and on the site of recurrence (chest wall: 43%; breast: 48%; regional node: 12%, p < 0.10). CONCLUSION: Like in the literature, severe recurrences are early recurrences, lymph node recurrences and recurrences following a primary tumour with involved axillary nodes.