[show abstract][hide abstract] ABSTRACT: This randomized phase II study was conducted to evaluate the efficacy of doxorubicin and docetaxel (DOC) administered either as a combination, an alternating or a sequential regimen in women with metastatic breast cancer. Secondary objectives included overall response, time to progression, survival and safety.
Patients with breast cancer (n=123) were randomized to receive doxorubicin and DOC either in combination (60 mg/m2 of each drug), or by alternated or sequential schedule (100 mg/m2 DOC and 75 mg/m2 doxorubicin) every 3 weeks for a maximum of eight cycles as first chemotherapy for stage IV disease. A second randomization allocated patients from each arm to receive prophylactic oral ciprofloxacin or no therapy to prevent febrile neutropenia.
Patients received a median of eight cycles. In an intention-to-treat analysis, the overall response was 63%, 52% and 61% in the combination, alternating and sequential schedules, respectively. Corresponding rates of complete response were 15%, 14% and 11%. Grade 4 neutropenia was common in all arms (81%) and, together with febrile neutropenia, was significantly more frequent with the combination. Prophylaxis with ciprofloxacin did not reduce the incidence of febrile neutropenia or infection. Other frequent non-hematological adverse events included alopecia, nausea, vomiting, stomatitis and asthenia. Congestive heart failure only occurred in the combination arm (10%).
All three schedules are feasible and endowed of good therapeutic activity. In view of the more pronounced toxicity and the risk of cardiac events because of the higher exposure to doxorubicin, the combination should be least favored when treating women with metastatic breast cancer. Prophylaxis with ciprofloxacin was ineffective and is not recommended.
Annals of Oncology 04/2004; 15(3):433-9. · 7.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Vitiligo patients possess high frequencies of circulating CD8+ T lymphocytes specific for the melanocyte differentiation antigen Melan-A/MART-1. These self-specific T cells exhibit intact functional properties and their T cell receptors are selected for a narrow range of high affinities of antigen recognition, suggesting their important role in the pathogenesis of vitiligo. In order to understand the molecular base for this unexpected, optimal T cell receptor recognition of a self-antigen, a tetramer-guided ex vivo analysis of the T cell receptor repertoire specific for the Melan-A antigen in a patient affected by vitiligo is reported. All T cell receptors sequenced corresponded to different clonotypes, excluding extensive clonal expansions and revealing a large repertoire of circulating Melan-A-specific T lymphocytes. A certain degree of T cell receptor structural conservation was noticed, however, as a single AV segment contributed to the alpha chain rearrangement in 100% of clones and a conserved amino acid sequence was found in the beta chain complementarity determining region 3 of various high affinity cells. We suggest that the conserved alpha chain confers self-antigen recognition, necessary for intrathymic selection and peripheral homeostasis, to many synonymous T cell receptors, whereas the beta chain fine tunes the T cell receptor affinity of the specific cells. In addition, we demonstrate that many high avidity T cell clones from this patient were capable of specifically lysing normal, HLA-matched melanocytes. These autoreactive clones persisted for more than 3 y in the patient's peripheral blood. These data, together with the skin-homing potential of the clones, directly point to the in vivo pathogenic role of melanocyte-specific cytotoxic T lymphocytes in vitiligo.
Journal of Investigative Dermatology 09/2003; 121(2):308-14. · 6.19 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this multicenter phase III trial was to assess the impact of a time-intensification of FEC (fluorouracil, epirubicin, cyclophosphamide) and MMM (mitoxantrone, methotrexate, mitomycin C) regimens, supported by lenograstim (G-CSF) on the objective response rate, time to progression and survival of patients with chemotherapy-naive metastatic breast cancer (mbc). Women with mbc were randomized to receive as first-line chemotherapy either standard-dose FEC (all doses in mg/m2): arm A (500, 75, 500 every 21 days), or time-intensified FEC-G: arm B (500, 75, 500 every 14 days), or time-intensified MMM-G: arm C (mitoxantrone 10, methotrexate 35 every 14 days and mitomycin C 10 every 28 days), both with support of lenograstim (G-CSF 150 microg/m2/day s.c. for 10 days). All study treatments were administered for six cycles. Eligible female patients were in the 31-70 year range with histologically proven mbc, and measurable or evaluable disease. An intent-to-treat analysis was performed. The overall response rate (CR + PR, intent-to-treat analysis) was significantly improved in the time-intensified FEC-G regimen (69%) in comparison with standard-dose FEC (41%), p=0.002. Time-intensified MMM-G (51%) did not lead to a significant improvement in the response rate. The percentage of complete responses was significantly higher in the FEC-G arm as compared to standard-dose FEC (17% vs. 4.7%; p=0.002). The median duration was longer in the intensified-dose arms without, however, achieving a statistically significant improvement. The median time to progression (TTP), and the median survival time did not differ between the three treatment arms. Grade 3-4 leukopenia was significantly higher (p<0.001) in the standard FEC regimen-treated patients. Thrombocytopenia was significantly higher (p<0.001) in both intensified regimens. Alopecia and mucositis were significantly more frequent in both anthracycline-containing regimens (p=0.003). Other hematological and non hematological toxicities were similar in the 3 treatment arms. The increase of dose-intensity of both FEC and MMM regimens improved activity, but not efficacy as compared to standard FEC regimen in our group of chemotherapy-naive, metastatic breast cancer patients.
[show abstract][hide abstract] ABSTRACT: Transient T cell immunodeficiency is a common complication following hematopoietic stem cell transplantation. In breast cancer patients transplanted with autologous peripheral blood progenitor cells (PBPC) harvested after cytotoxic treatment with either cyclophosphamide or epirubicin plus paclitaxel, we evaluated T cells infused in grafts and in peripheral blood during the early reconstitution phase. We found that PBPC grafts harvested after treatment with epirubicin plus paclitaxel contained substantially larger numbers of T cells with less altered composition than after cyclophosphamide. Three months after high-dose cytotoxic chemotherapy, the numbers and the kinetics of circulating naive T cells, but not of memory and CD28- T cells, correlated positively with the number of naive T cells infused PBPC grafts. Finally, retrospective analysis of two cohorts of patients transplanted in different clinical settings with PBPC grafts harvested following cyclophosphamide or epirubicin plus paclitaxel showed apparently different susceptibilities to develop endogenous varicella zoster virus reactivation in the first year after high-dose cytotoxic chemotherapy. On the whole, these data indicate that number and composition of T cells in PBPC grafts vary according to the former cytotoxic therapy, and suggest that autologous transfer of T cells may accelerate the early T cell reconstitution phase and possibly ameliorate immune competence in patients rendered lymphopenic by high-dose chemotherapy.
Bone Marrow Transplantation 02/2003; 31(1):31-8. · 3.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: TCR-alpha and -beta chains are composed of somatically rearranged V, D, and J germline-encoded gene segments that confer Ag specificity. Recent crystallographic analyses revealed that TCR-alpha has more contacts with peptide than TCR-beta, suggesting the possibility that peptide recognition predominantly relies on TCR-alpha. T cells specific for the self Ag Melan-A/MART-1 possess an exceptionally high precursor frequency in human histocompatibility leukocyte Ag-A2 individuals. This provided a unique situation for assessment of the structural relationship between TCR and peptide/MHC ligand at both the pre- and postimmune levels. Molecular and phenotypic analysis of many different Melan-A-specific T cell populations revealed that a structural constraint is imposed on the TCR for engagement with Melan-A peptides presented by HLA-A2, namely the highly preferential use of a particular TCRAV segment, AV2. Examination of CD8 single-positive thymocytes indicated that this preferential use in forming the Melan-A-specific TCR is mainly imposed by intrathymic positive selection. Our data demonstrate a dominant function of TCRAV2 segment in forming the TCR repertoire specific for the human self Ag Melan-A/MART-1 and support the view that Ag recognition is mediated predominantly by TCR-alpha.
The Journal of Immunology 01/2003; 169(11):6253-60. · 5.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: Modifications in tumour antigen-derived epitopes that stabilize the major histocompatibility complex (MHC)-peptide complex result in enhanced stimulatory capacity and improved immunogenicity of the altered peptide. These epitope analogues are attractive candidates for the development of peptide-based vaccine trials. Any modification, however, in tumour antigens may induce T-cell responses that could either fail to react against the naturally occurring peptides or represent only a subset of the total antigen-specific repertoire. In the present study, we performed a critical analysis of the ability of cytotoxic T-lymphocyte (CTL) clones, derived from two melanoma patients through stimulation with the A27L peptide analogue, to cross-react with the naturally processed Melan-A/MART-1 (Melan-A) peptides in terms of T-cell receptor (TCR) affinity, functional avidity and fine antigen specificity. We found that all the A27L-specific clones analysed possessed a very low avidity for the natural Melan-A peptides, and that their binding affinity for human leukocyte antigen (HLA) tetramers complexed with both the modified and the natural Melan-A peptides did not strictly correlate with their functional avidity. We also observed that these clones were able to cross-recognize both natural Melan-A peptides in one patient, but only one peptide in the second patient. We discuss the capability of the A27L peptide analogue to stimulate all the available Melan-A-specific repertoire.
Melanoma Research 11/2002; 12(5):491-8. · 2.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: We studied concentration, phenotype, and function of peripheral blood (PB) dendritic cells (DCs) from patients with multiple myeloma (MM). The absolute number of circulating precursors of myeloid and plasmacytoid DCs was significantly lower in MM patients than in healthy subjects. After maturation, PBDCs from MM patients showed significantly lower expression of HLA-DR, CD40, and CD80 antigens and impaired induction of allogeneic T-cell proliferation compared with controls. Remarkably, they were not capable of presenting the patient-specific tumor idiotype to autologous T cells. Conversely, DCs generated in vitro from CD14(+) monocytes from the same patients, and PBDCs freshly isolated from healthy donors efficiently stimulated allogeneic and autologous T cells. To clarify the mechanism of PBDC deficiency in MM, we investigated the effects of the main plasma cell growth factor, interleukin-6 (IL-6), on the development of DCs from CD34(+) cells. IL-6 inhibited the colony growth of CD34(+) DC progenitors and switched the commitment of CD34(+) cells from DCs to CD14(+) CD1a(-) CD86(-)CD80(-) CD40(+/-)HLA-DR +/- monocytic cells exerting potent phagocytic activity but no antigen-presentation capacity. This effect was reversed by anti-IL-6 antibodies. Growing CD34(+) cells in the presence of autologous serum (without IL-6) also suppressed the development of functional DCs. This study demonstrates that PBDCs from MM patients are functionally defective, partially because of IL-6-mediated inhibition of development. This brings into question the advisability of using PBDCs as antigen carriers for immunotherapy trials in MM. The results also suggest a novel mechanism whereby myeloma cells escape immune recognition.
[show abstract][hide abstract] ABSTRACT: To assess the efficacy of primary single-agent epirubicin (120 mg/m(2) every 3 weeks for three cycles) in reducing tumor burden in operable breast cancer >or=2.5 cm in largest diameter at diagnosis and its effect on the rate of conservative surgery.
A total of 319 eligible patients, who were all candidates for mastectomy, were enrolled on to a multicenter prospective non-randomized study. Tumor response was assessed clinically and pathologically. Relapse-free and overall survival were assessed on major prognostic variables.
After primary epirubicin, complete disappearance of invasive neoplastic cells accounted for only 2.6% of patients, but 40% of patients had their primary tumor downstaged to <or=2 cm in diameter. Conservative surgery was performed in 67% of patients. At a median follow-up of 5 years, both primary tumor size at diagnosis (P <0.01) and pathological nodal involvement (P <0.01) significantly influenced treatment outcome. After conserving surgery and breast irradiation, local recurrences accounted for approximately 4% of patients.
This multicenter study confirms that three cycles of full-dose epirubicin can avoid mutilating surgery in a high proportion of patients with tumors not amenable to primary conservative surgery. This multimodal treatment can be safely administered outside of clinical trials in patients presenting with large tumors and with a desire to preserve their body integrity.
Annals of Oncology 07/2002; 13(7):1049-58. · 7.38 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recovery of total T cell numbers after in vivo T-cell depletion in humans is accompanied by complex perturbation within the CD8+ subset. We aimed to elucidate the reconstitution of CD8+ T cells by separate analysis of putative naïve CD95- CD28+, memory CD95+ CD28+ and CD28- T cell compartments after acute maximal depletion by high-dose chemotherapy (HD-ChT) in women with high-risk breast cancer. We found that recovery of putative naïve CD8+ CD95- CD28+ and CD4+ CD95- CD28+ T cells, was compatible with a thymus-dependent regenerative pathway since their recovery was slow and time-dependent, their values were tightly related to each other, and their reconstitution patterns were inversely related to age. By analysing non-naïve T cells, a striking diversion between putative memory T cells and CD28- T cells was found. These latter increased early well beyond normal values, thus playing a pivotal role in total T-cell homeostasis, and contributed to reduce the CD4 : CD8 ratio. In contrast, putative memory T cells returned to values not significantly different from those seen in patients at diagnosis, indicating that this compartment may recover after HD-ChT. At 3-5 years after treatment, naïve T cells persisted at low levels, with expansion of CD28- T cells, suggesting that such alterations may extend further. These findings indicate that CD28- T cells were responsible for 'blind' T-cell homeostasis, but support the notion that memory and naïve T cells are regulated separately. Given their distinct dynamics, quantitative evaluation of T-cell pools in patients undergoing chemotherapy should take into account separate analysis of naïve, memory and CD28- T cells.
[show abstract][hide abstract] ABSTRACT: The immune-mediated graft-versus-tumor (GVT) effect plays a therapeutic role in the treatment of patients with hematologic malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT). More recently, it was reported that a GVT effect also occurred in patients who underwent transplantation for metastatic renal carcinoma. The authors carried out a pilot trial of allogeneic transplantation after a reduced-intensity, preparative regimen in patients with refractory malignancies, including solid tumors. The objectives of the current study were to evaluate the feasibility of this approach in terms of toxicity and engraftment and to document evidence of GVT effects.
Seventeen patients with Stage IV malignancies (7 patients with renal cell carcinoma, 3 patients with sarcoma, 2 patients with breast carcinoma, 2 patients with Hodgkin disease, 1 patient with ovarian carcinoma, 1 patient with melanoma, and 1 patient with both melanoma and renal cell carcinoma) that were not amenable to further conventional treatment were enrolled. The median patient age was 43 years (range, 10-60 years). The Eastern Cooperative Oncology Group performance status (PS) was 0-1 in 11 patients and 2-3 in 6 patients. Preparative treatment consisted of reduced-intensity chemotherapy with fludarabine (30 mg/m(2) per day for 4 consecutive days) and cyclophosphamide (30 mg/Kg per day for 2 consecutive days) prior to allogeneic HSCT from a human leukocyte antigen-identical sibling. The median number of CD34+ cells infused was 6.06 x 10(6)/kg (range, 1.5-14.0 x 10(6)/kg). Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin-A and short-term methotrexate.
Patients who had a PS of 2-3 prior to undergoing HSCT experienced Grade 4 hematologic toxicities and Grade > or = 3 organ toxicities and died of either treatment-related complications or disease progression within 100 days from transplantation. By contrast, 10 of 11 patients who had a PS of 0-1 prior to undergoing HSCT experienced only short-lasting, Grade < or = 3 neutropenia and thrombocytopenia and no organ toxicity; 1 of 10 patients died of graft failure on Day +29 after undergoing HSCT. By Day +90, 100% donor chimerism was documented in all patients with a past history of heavy chemotherapy, whereas mixed donor chimerism was observed in the 4 patients with a past history of only 1 line of chemotherapy and/or immunotherapy prior to entering the HSCT program. Grade 2-3 acute GVHD occurred in 5 patients. Among patients with a follow-up > 100 days, 2 complete responses and 3 transitory partial responses were recorded.
With this conditioning regimen, full donor chimerism was achieved rapidly only in patients who had received previous intensive chemotherapy. In a proportion of patients with refractory malignancies, allogeneic transplantation resulted in tumor regression. This novel therapeutic strategy may provide little benefit in patients with poor PS and rapidly progressing disease.
Cancer 05/2002; 94(9):2409-15. · 5.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: The purpose of this study was to evaluate the efficacy and tolerability of single-agent gemcitabine in untreated elderly patients with stage IIIb/IV non-small-cell lung cancer (NSCLC). Since April 1997, 46 consecutive patients have been enrolled in this multicenter study. Gemcitabine 1,000 mg/m2 was administered as a 30-minute intravenous infusion on days 1, 8, and 15 every 28 days. Primary patient characteristics were: male/female 38/8; median age 73 years (range: 70-82 years); median Karnofsky performance status (PS) 90 (range: 70-100); stage IIIb 61% and stage IV 39%; histotype: epidermoid 48%, adenocarcinoma 43%, and large cell carcinoma 9%. No complete response was observed, but 10 (21.7%) patients achieved partial response (PR) (95% confidence limits: 11-36%), 27 (58.7%) had stable disease (SD), and 7 (15%) progressed early (at the first evaluation). The median duration of PR and SD was 8 months (range: 4-23+ months) and 4 months (range: 2-9 months), respectively. Subjective response evaluating PS and symptoms such as dyspnea, pain, and cough was evaluated in 40 patients; 11 (27.5%) improved, 15 (37.5%) remained stable, and 14 (35%) worsened. The median time to progression was 4 months, the median survival was 9 months, and 1-year survival was 44%. After a median follow-up of 10.5 months, 14 patients are still alive. There were no grade 4 toxicities. Grade 3 neutropenia and thrombocytopenia occurred in 19% and 2% of patients, respectively. Nonhematologic toxicities were mild. Grade I/II side effects of nausea/vomiting, transient fever, increase of hepatic transaminases, transient peripheral edema at lower extremity (not related to cardiac or renal disease or phlebothrombosis) were reported. This phase II study confirms the activity and favorable toxicity profile of single-agent gemcitabine in the treatment of elderly patients with advanced NSCLC.
American Journal of Clinical Oncology 01/2002; 24(6):614-7. · 2.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: In peripheral blood, myeloid markers identify a heterogeneous mixture of cells in transit from the bone marrow to peripheral tissues. Similarly, HLA-class II DR expression usually identifies mononuclear cells with the potential for developing antigen-presenting activity. We gathered putative antigen presenting cells bearing myeloid markers (My-APC) to study their composition by cell surface phenotype.
To gather and dissect My-APC phenotype while excluding lymphocytes and granulocytes, we developed a strategy based on staining red cell-lysed peripheral blood and gating cells bearing myeloid markers and physical parameters of large mononuclear cells.
Phenotypic analysis within the My-APC gate showed three distinct populations. The largest fraction was constituted by CD14+ monocytes that extended into the other two populations, each expressing gradually lower levels of CD14 surface antigen along with increasing levels of CD16 and CD2, respectively. The CD16 and CD2 expression patterns extended from CD16+CD14+ or CD2+CD14+ double- positive intermediate cells toward each single positive subset, but they were reciprocally exclusive. Interestingly, CD2+CD14- cells within the My-APC gate were equivalent to myeloid dendritic cell precursors (pre-DC) defined previously by the absence of lineage markers and expression of HLA-DR and myeloid markers. Phenotypic analysis of each population revealed differences in the expression of costimulatory molecules and CD62L.
This novel analytical approach allowed us to distinguish circulating My-APC in three subsets and to identify relationships between monocytes and other related myeloid populations including DC.
[show abstract][hide abstract] ABSTRACT: Fifty consecutive patients with stage IIIB-IV non-small cell lung cancer (NSCLC) received the ICE regimen at intermediate doses (ifosfamide 1 g/m2, carboplatin 120 mg/m2, etoposide 80 mg/m2, day 1 to 3, q.4 weeks, for a maximum of 6 cycles). Overall 2 complete response (CR) and 10 partial response (PR) (overall response, OR: 24%, 95% C.I. 14-37%) were observed. An additional 7 patients had stable disease (SD) lasting more than 6 months, therefore a clinical benefit (CR+PR+SD >6 mos) was achieved in 19 patients (38%). Median time-to-progression (TTP) was 7 months and median overall survival (OS) was 11 months; 1- and 2-year survival rates were 36% and 10%. The ICE regimen was well tolerated and devoid of any cardiac, hepatic or neurologic toxicity. Moderate nausea and vomiting were easily manageable, grade 2 alopecia was universal, while hematological toxicity was mild (grade 2 leuko- and thrombocytopenia). Due to its efficacy and safety profile, this 3-drug regimen can be considered for routine community use.
[show abstract][hide abstract] ABSTRACT: Cancer immunotherapy is still largely confined to the laboratory bench and experimental animal models. Yet the field is rapidly moving forward and some immunological tools are now entering into clinical use. The first and perhaps best example of such progress is given by bioengineered humanized monoclonal antibodies of which some have been already approved for therapy in B-cell lymphoma and breast cancer. Unexpectedly, another remarkable form of immunotherapy has turned out to derive from T-cell adoptive therapy associated with allogeneic bone marrow transplantation. Its benefits render such an approach the first choice therapy for a large number of hematological malignancies and it is now being adapted also for treatment of advanced solid tumors. Finally, harnessing the immune system against the autologous tumor remains the most ambitious but still distant design for immunotherapy. Recent technical advances and a better understanding of the immune system in cancer patients should concur in defining the best strategy for active immunotherapy in clinical oncology.
[show abstract][hide abstract] ABSTRACT: While tumor-associated antigen (TAA)-specific CD8(+) T lymphocytes have been detected in metastatic melanoma patients, immune response in early disease phases has not yet been carefully evaluated. We looked for circulating cytotoxic T lymphocytes (CTL) directed against Melan-A / MART1, tyrosinase, gp100 and MAGE-3 antigens in patients with a diagnosis of primary cutaneous melanoma by using fluorescent HLA-A2 tetramers. In five out of six cases high numbers of CD8(+)/tetramer(+) cells could be detected by flow cytometry, and in four patients lymphocyte populations specific for two different melanoma antigens (Melan-A/MART1 and tyrosinase) were contemporaneously present. The TAA-specific cells could represent as much as 1/220 T lymphocytes in the circulating CD8(+) population. When tetramers were used to monitor the in vitro expansion of TAA-specific CTL precursors upon antigen-specific stimulation, a diverse expansion potential was evidenced in CTL from the different donors and, more strikingly, in CTL specific for the different TAA. Melan-A/MART1-specific CTL clones derived from two patients exhibited a broad range of avidity. Only the highest avidity clones, representing about 50 % of the cases analyzed, were tumor specific. By correlating tetramer staining with clone avidity, we found that tetramer fluorescence intensity could represent a good indicator of TCR affinity, but not of overall clone avidity.
European Journal of Immunology 03/2001; 31(2):412-20. · 4.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: While tumor-associated antigen (TAA)-specific CD8+ T lymphocytes have been detected in metastatic melanoma patients, immune response in early disease phases has not yet been carefully evaluated. We looked for circulating cytotoxic T lymphocytes (CTL) directed against Melan-A / MART1, tyrosinase, gp100 and MAGE-3 antigens in patients with a diagnosis of primary cutaneous melanoma by using fluorescent HLA-A2 tetramers. In five out of six cases high numbers of CD8+ / tetramer+ cells could be detected by flow cytometry, and in four patients lymphocyte populations specific for two different melanoma antigens (Melan-A / MART1 and tyrosinase) were contemporarily present. The TAA-specific cells could represent as much as 1 / 220 T lymphocytes in the circulating CD8+ population. When tetramers were used to monitor the in vitro expansion of TAA-specific CTL precursors upon antigen-specific stimulation, a diverse expansion potential was evidenced in CTL from the different donors and, more strikingly, in CTL specific for the different TAA. Melan-A / MART1-specific CTL clones derived from two patients exhibited a broad range of avidity. Only the highest avidity clones, representing about 50 % of the cases analyzed, were tumor specific. By correlating tetramer staining with clone avidity, we found that tetramer fluorescence intensity could represent a good indicator of TCR affinity, but not of overall clone avidity.
European Journal of Immunology 01/2001; 31(2):412 - 420. · 4.97 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aims of the study were the identification and optimization of the radiation protection measures for in-patients who underwent palliative radionuclide therapy for bone metastases with 153Sm-EDTMP activities lower than 3 GBq. The suitability of the preventive procedures from the contamination of places and objects, and for the protection of the hospital staff, other patients and relatives from the danger of external radiation and internal contamination has been evaluated by carrying out a series of measurements both of superficial contamination inside the confinement room and of the dose near the treated patients. The results show that the contamination of the places and the objects close to treated patients is really low. The greatest risk of contamination depended on the management of the physiological waste that, therefore, should be collected and disposed as radioactive one. The measurements of external radiation show that nearby the confinement room the dose limit for public is not exceeded. The same is true for the dose limit of 3 mSv established for relatives who, when taking care treated patients, receive a dose lower than 20 microSv a patient. The fulfillment of the proposed radiation protection measures assures the containment of the risk of exposure and contamination for nursing and medical staff involved in radionuclide-based therapy.
Giornale italiano di medicina del lavoro ed ergonomia 01/2001; 23(4):435-7.
[show abstract][hide abstract] ABSTRACT: Anthracyclines-taxanes containing regimens are widely used for breast cancer treatment both in neoadjuvant-adjuvant setting and in metastatic disease. Recently high-dose chemotherapy (HDC) with autologous stem cell support has been introduced as adjuvant treatment for high-risk primary breast cancer and for selected subsets of women with metastatic disease. Therefore, salvage treatment for previously treated patients with progressive disease becomes even more problematic. A regimen of continuous infusion of fluorouracil (FU) and vinorelbine (VNR) has been evaluated in heavily pretreated metastatic breast cancer patients.
Forty-eight women, median age 52 years, with previously treated breast cancer entered the study. All but one received more than one line of prior systemic chemotherapy for metastatic disease. Furthermore 14 women had undergone HDC with peripheral blood progenitor cells transplantation in adjuvant setting (6 pts), or metastatic disease (8 pts). Treatment consisted of four-day infusion of FU (1000 mg/m2/day) plus VNR (20 mg/m2/i.v. day 1 and 5), recycled every 3 weeks for a total of six courses. Drugs administration was discontinued for G4 toxicity, tumor progression or patient's refusal.
Twenty PR and four CR for an overall response rate of 50% (95%C.I. 36-64%) were recorded. The therapeutic efficacy of the tested regimen was documented both in patients unresponsive to previous anthracyclines-taxanes combinations and in those relapsing after HDC. The median duration of response was 9 months and median survival 16 months. One third of patients experienced Grade-3 stomatitis-mucositis, hematological toxicity was mild and no cardiac toxicity was observed. Twenty-five women (52%) suffered from infusion-related phlebitis (in half of patients a central venous device was necessary at some point of the treatment program).
The combination of FU infusion and VNR i.v. is an effective salvage treatment for heavily pretreated metastatic breast cancer patients, and may represent a valid alternative when other cytotoxic regimens are not feasible.
Breast Cancer Research and Treatment 07/2000; 61(3):241-7. · 4.47 Impact Factor
[show abstract][hide abstract] ABSTRACT: Because tumor contamination of hematopoietic stem cell grafts may influence the outcome in breast carcinoma (BC) patients undergoing high dose chemotherapy (HDC), several ex vivo procedures for the purging of autologous harvests have been investigated. The authors studied the presence of epithelial tumor cells and the growth of hematopoietic progenitors in peripheral blood stem cell (PBSC) collections from patients with metastatic breast carcinoma before and after a purging procedure performed by a negative immunomagnetic BC cell separation.
Eighteen patients entered the study. Tumor contamination was assessed by conventional immunocytochemistry (ICC) and by a liquid culture assay developed in the study laboratory. Committed and more primitive hematopoietic progenitors were quantitated before and after the negative selection. Ten patients received HDC with purged PBSC support.
Before purging, 4 of 18 PBSC collections were found to be contaminated by liquid culture; among these samples, only 1 was positive by ICC. Three of the four positive collections, including the ICC positive sample, became negative after immunomagnetic selection whereas BC cells still were present after the procedure in one harvest. A high recovery of both primitive and mature hematopoietic progenitors was found after the purging procedure. Patients receiving purged PBSC after myeloablation had a prompt and complete hematopoietic reconstitution, and no graft failure was observed at a median follow-up of 1 year.
The preliminary results of the current study suggest that negative selection of BC cells is able to purge PBSC effectively while having no apparent affect on hematopoietic progenitor recovery in vitro and in vivo.
Cancer 07/2000; 88(12):2758-65. · 5.20 Impact Factor