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At least 847 records · Page 47Linked to original sources
PubMed2003

Pilot evaluation of high-dose carboplatin and paclitaxel followed by high-dose melphalan supported by peripheral blood stem cells in previously untreated advanced ovarian cancer: a gynecologic oncology group study.

OBJECTIVES: To evaluate the efficacy and safety of multiple cycles of high-dose carboplatin and paclitaxel and one consolidation cycle of high-dose melphalan with all cycles supported by hematopoietic stem cells and cytokine, in previously untreated patients with optimally debulked stage III epithelial ovarian cancer. PATIENTS AND METHOD: Patients had histologically documented epithelial ovarian cancer and optimal initial cytoreductive surgery. No prior chemotherapy was permitted. Adequate performance status, bone marrow, hepatic, and renal function was required. After being mobilized with cyclophosphamide 3 g/m(2), paclitaxel 300 mg/m(2), and filgrastim 5 microg/kg/day, peripheral blood stem cells (PBSC) were collected by leukapheresis. Patients received three cycles of carboplatin AUC 15 mg. min/ml iv, paclitaxel 250 mg/m(2), and PBSC with filgrastim every 28 days, followed by one cycle of melphalan 140 mg/m(2) and hematopoietic support. RESULTS: Nine patients entered the trial and received all planned cycles of chemotherapy. Of the eight patients who consented to surgical reassessment upon completing therapy, four had residual small-volume macroscopic disease, three had microscopic residual disease, and one had pathologic complete response. The estimated probability of a pathologic complete response was 12.5% (95% confidence interval: 0.3-52.7%). Hematologic toxicity was severe but manageable. Eleven of 45 cycles (24.4%) resulted in hospital admission for neutropenic fever, dehydration +/- diarrhea, syncope, or shortness of breath and pain secondary to tense ascites. CONCLUSIONS: The low pathological complete response rate did not justify toxicity; thus, the study was closed. High-dose chemotherapy as first-line treatment for epithelial ovarian cancer remains experimental and should be restricted to clinical trials.

Adult↗
PubMed1995

[Mega-dose chemotherapy with peripheral blood stem cell transplantation (PBS-CT) for small cell lung cancer (SCLC)].

Feasibility and the efficacy of mega-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) for small cell lung cancer (SCLC) were evaluated. Autologous peripheral blood stem cell (APBSC) was collected after induction chemotherapy (Extensive disease: CDDP+etoposide+ADM, Limited disease: CDDP+etoposide) followed by the administration of granulocyte colony stimulating factor (G-CSF). Five cases of ED and 2 cases of LD have been entered in the protocol so far. PBSC was harvested after the second course of induction chemotherapy, and a sufficient number of PBSC (CFU-GM > or = 1 x 10(5)/kg) could be harvested and cryopreserved in all 7 cases. After completion of 4 courses of induction chemotherapy, three patients who achieved CR or good PR were treated by the combination of CBDCA (1,600 mg/m2) plus etoposide (1,600 mg/m2) followed by APBSCT and G-CSF. Hematologic recovery after APBSCT was rapid (absolute granulocyte count > 500/microliters: 9-11 day, Plt > 3 x 10(4)/microliters:10-14 day) and no infectious episode nor bleeding tendency occurred throughout the treatment period. Although grade 3 gastrointestinal toxicity was seen in one patient, the mega-dose chemotherapy with APBSCT in SCLC was considered safe and feasible. Further clinical trials are needed to establish the role of mega-dose chemotherapy for the treatment of SCLC.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

High dose chemotherapy with cisplatin, VP16 and carboplatin with stem cell support in patients with advanced ovarian cancer.

Authors treated 4 patients suffering from advanced ovarian cancer with high-dose chemotherapy and autologous peripheral blood stem cell (APBSC) or autologous bone marrow stem cell (ABM) as hematopoietic support. In three patients were collected peripheral blood stem cells using a fully automated blood cell separator during hematopoietic recovery following aplasia induced by non-intensive chemotherapy (cisplatin 200 mg/m2 and cyclophosphamide 1,500 mg/m2). Hemopoietic reconstitution of the four patients submitted to APBSC or ABM support after high-dose chemotherapy (cisplatin 100 mg/m2, VP16 650 mg/m2 and carboplatin 1,800 mg/m2) showed the low hematological toxicity of our treatment with APBSC support. Moreover, the drug combination of cisplatin and cyclophosphamide has clinical activity in ovarian cancer and it is an optimal association to mobilize and harvest large number of PBSC.

Adult↗
PubMed1998

High-dose chemotherapy with autologous stem cell support in patients with responding stage IV breast cancer.

Ninety-four patients underwent high-dose chemotherapy with stem cell support for stage IV breast cancer. The high-dose chemotherapy consisted of the Stamp V regimen in all patients comprising cyclophosphamide, thiotepa and carboplatin (CTCb). Twenty-three patients received sequential high-dose therapies with the first consisting of high-dose melphalan and the second of Stamp V. Two patients died from chemotherapy-related complications resulting in a transplant-related mortality at 100 days of 2.2%. The progression-free survival at 3 years was 36% in patients with no evidence of disease at the first course of high-dose therapy compared with 17% in patients with remaining disease at time of the high-dose therapy (P = 0.03). There was no difference in overall survival between patients with no evidence of disease and other patients. The source of stem cells, single or double courses of high-dose therapy, positive selection of CD34+ cells, or number of involved sites had no influence on either progression-free survival or overall survival. Further studies of more intensive induction chemotherapy followed by high-dose therapy with stem cell support are indicated.

Adult↗
PubMed1993

Role of high-dose chemotherapy and autologous stem cell support in treatment of breast cancer.

Patients with metastatic breast cancer with chemotherapy-sensitive disease, good performance status, and few sites of metastatic disease are the best candidates for high-dose chemotherapy and autologous stem cell reinfusion. Even in this selected subset of patients with metastatic breast cancer, at best 30% to 40% will maintain a complete remission beyond 2 years. In the high-risk adjuvant setting, high-dose chemotherapy appears efficacious; however, results from ongoing randomized prospective trials will not be available for several years.

Antineoplastic Agents↗
PubMed1988

Biologically motivated two-stage model for cancer risk assessment.

A model for carcinogenesis is presented that incorporates two features: (1) transition of target stem cells into cancer cells via an intermediate stage in two irreversible steps, and (2) growth and differentiation of normal target and intermediate cells. Implications of the model for initiation-promotion and environmental carcinogenesis are considered.

Animals↗
PubMed2006

Connecting cancer to the asymmetric division of stem cells.

Two studies, one in this issue of Cell and the other in Developmental Cell show that the cell-fate determinant Brain Tumor (Brat) suppresses self-renewal in one of the daughter cells that arise from the asymmetric division of a neural stem cell. This work suggests a mechanism by which loss of polarity in stem cells may lead to tumorigenesis.

Animals↗
PubMed2006

Order of patient entry influences outcome for metastatic renal cell cancer after non-myeloablative allogeneic stem cell transplantation.

Allogeneic transplantation for renal cell carcinoma has shown encouraging preliminary results. We reviewed the published literature to evaluate the impact of patient selection. Most studies did not include information on prognostic factors. We used patient entry rank within individual studies as a novel surrogate for patient selection, motivated by our own experience of an apparent impact of entry rank. One hundred patients were identified from nine studies. Twenty-six per cent of patients demonstrated either a partial or complete response. Median overall survival was 12.3 months. Grade 2-4 acute graft-versus-host disease correlated with an increased likelihood of response (odds ratio: 5.4, 95% confidence interval: 1.6-18.1, P = 0.006) but not survival. Earlier patient entry rank on each trial was associated with a higher probability of response (P = 0.004) and superior survival (P = 0.004). Patient entry rank served as a powerful prognostic factor, suggesting bias in patient selection that evolved over the course of the study. Further studies are warranted to determine the influence of order of patient entry in other early clinical trial settings.

Acute Disease↗
PubMed1996

Double dose-intensive chemotherapy with autologous stem-cell support for metastatic breast cancer: no improvement in progression-free survival by the sequence of high-dose melphalan followed by cyclophosphamide, thiotepa, and carboplatin.

PURPOSE: Twenty-one percent of responding metastatic breast cancer patients remain progression-free a median 50 months following one intensification cycle of cyclophosphamide (6,000 mg/m2), thiotepa (500 mg/ m2), and carboplatin (800 mg/m2) (CTCb) with autologous bone marrow transplantation (ABMT). This trial studied whether the sequence of high-dose melphalan followed by CTCb resulted in improved disease response and duration. METHODS: Women with at least partial responses (PRS) to induction received melphalan (140 or 180 mg/ m2) with peripheral-blood progenitor cell (PBPC) and granulocyte colony-stimulating factor (G-CSF) support. They were monitored as outpatients. After recovery, patients were hospitalized for CTCb with marrow, PBPC, and G-CSF support. RESULTS: Data on 67 women, at a median of 25 months from CTCb, were examined. After melphalan, 49 (73%) required admission for fever (89%), mucositis (35%), or infection (15%) (median stay, 8 days). All received CTCb. For the first 33 patients, the median days from start of melphalan to CTCb was 24. After liver toxicity (one death from venoocclusive disease [VOD]) developed in 11 patients during CTCb, the interval between intensifications was increased to 35 days without incident. Twenty-three patients (34%) are progression-free a median of 16 months post-CTCb. The median progression-free survival (PFS) and survival times for the whole group are estimated at 11 and 20 months, respectively. CONCLUSION: Treatment with this sequence of high-dose melphalan followed by CTCb has not resulted in superior PFS to date, when compared with single-intensification CTCb. This report discusses factors related to patient selection, the role of induced drug resistance, and the schedule of administration of alkylating agenting that may adversely influence outcome.

Adolescent↗
PubMed2001

Soluble Fas (CD95) is a prognostic factor in patients with metastatic breast cancer undergoing high-dose chemotherapy and autologous stem cell transplantation.

The Fas/Fas ligand (FasL) system plays an important role in cellular apoptosis and is involved in cancer cell death induced by the immune system and anticancer drugs. Increased serum levels of soluble Fas (sFas) are associated with a number of different disease states and with tumor progression and metastasis in patients. In this study, we examined the plasma levels of sFas in 94 women with metastatic breast cancer undergoing high-dose chemotherapy (HDCT) treatment with autologous stem cell transplantation (ASCT) using a quantitative enzyme-linked immunosorbent assay (ELISA) method. Thirty-one patients (31/94, 33%) had plasma sFas levels greater than the optimum cut point of 1.90 ng/ml (median 2.47, range 1.98-13.54 ng/ml) and were designated as sFas positive. Sixty-three patients (63/94, 67%) had sFas levels below 1.90 ng/ml (median 1.14, range 0.47-1.89 ng/ml). In univariate analysis, patients with sFas-positive status, HER-2 overexpression, and the presence of liver metastases had a significantly shorter time to disease progression (PFS) and significantly decreased overall survival (OS). Multivariable analysis (Cox proportional hazards model) for PFS determined that sFas status significantly predicted disease progression (p = 0.004) with an adjusted hazard ratio (HR) of 2.0 (95% CI, 1.3-3.3). HER-2 status and liver metastases were also significant independent predictors of disease progression (p < 0.001) for both. sFas level was also an independent prognostic factor for OS with an adjusted HR of 2.0 (p = 0.006; 95% CI, 1.2-3.4). HER-2 status and liver metastases also remained highly significant independent prognostic factors for OS (HER-2: p < 0.001, HR 2.3, and liver metastases: p = 0.001, HR 2.7). In conclusion, these results suggest that plasma levels of sFas may be a valuable clinical prognostic factor in predicting outcome (PFS and OS) for patients with metastatic breast cancer undergoing HDCT with ASCT.

Adult↗
PubMed2001

Comparison of interleukin-12 with lung cancer and malignant lymphoma undergoing autologous peripheral blood stem cell transplantation.

PURPOSE: High-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for solid tumors including lung cancer. METHODS: We measured IL-12 levels in patients with lung cancer undergoing autologous PBSCT in order to elucidate the role of IL-12 in immune response recovery following stem cell transplantation. RESULTS: Compared to IL-12 levels at 1 week after PBSCT for lung cancer patients, those at 3 weeks were significantly increased ( P<0.01). In contrast, serum IL-12 levels in malignant lymphoma patients did not change significantly. There were no significant differences in levels of other cytokines between 1 week and 3 weeks after transplantation in patients with lung cancer. The frequency of helper/inducer T cells was increased in peripheral blood 1 week after transplantation in both lung cancer and malignant lymphoma patients. There was a significant increase in activated T cell numbers following PBSCT. Furthermore, high levels of other activated T cells persisted in the post-PBSCT period in patients with lung cancer and the number of cytotoxic T cells significantly increased. Natural killer (NK) cell numbers also tended to increase, although that of malignant lymphoma was not significant. A strong correlation was observed between serum IL-12 levels and NK cell numbers and interferon-gamma levels in lung cancer not but in malignant lymphoma patients. The analysis of transfused PBSC showed that the numbers of granulocyte/macrophage colony-forming units were similar in lung cancer and malignant lymphoma patients. However, the number of CD34+ cells was significantly higher in lung cancer than in malignant lymphoma patients. All of the CD34+ subpopulations were lower in percentage in patients with lung cancer than in patients with malignant lymphoma. In particular, the CD34+ CD33- subpopulation was significantly lower in percentage in lung cancer patients. CONCLUSION: Our findings suggest that PBSC in lung cancer are potent mediators of anticancer activity and that they might play an immunotherapeutic role against autologous malignant cells.

Adult↗
PubMed1991

Autologous blood stem cell harvesting and transplantation in patients with advanced ovarian cancer.

We investigated the feasibility of a programme of autologous blood stem cell (ABSC) harvesting and transplantation in 13 patients with advanced ovarian cancer, previously untreated by chemotherapy or radiotherapy and entering a phase II study of high-dose cisplatin, etoposide and carboplatin with haematopoietic stem cell rescue. Prior to high-dose treatment all patients underwent two courses of cisplatin and cyclophosphamide. An 8-fold increase of the peripheral colony forming unit granulocytic-macrophage (CFU-GM) was observed during recovery from myelosuppression after the first chemotherapy course. The second course determined a 2.5-fold increase of peripheral CFU-GM. In 70% of enrolled patients (nine patients) we were able to perform ABSC harvesting by leukaphereses; in the apheresed patients we harvested an average of 20.8 x 10(4)/kg CFU-GM (range 10.9-37.0). Haematopoietic trilineage engraftment, established as the number of days necessary to reach white blood cells (WBC) greater than 1.0 x 10(9)/l, polymorphonuclear leucocytes (PMN) greater than 0.5 x 10(9)/l and platelets (PLT) greater than 50 x 10(9)/l, occurred very promptly and was sustained in the same series after high-dose cisplatin, carboplatin and etoposide, followed by autologous blood stem cell transplantation (ABSCT). In our experience we found a significant correlation (r = 0.77; P less than 0.05) between CFU-GM infused dose and the engraftment speed of PMN. We conclude that the combination of cisplatin and cyclophosphamide is effective in mobilizing haematopoietic progenitors in the peripheral blood of patients with advanced ovarian cancer, previously untreated by chemoradiotherapy. Moreover, ABSCT is capable of rapidly restoring the haematopoietic function after high-dose treatment and for this reason it represents a particularly advisable therapeutic option for the treatment of solid tumours because these patients are commonly older than 50 and can be excluded from bone marrow transplantation.

Adult↗