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Biomedical subjects

A Gennari

Publications and source records attributed to A Gennari.

At least 19 recordsLinked to original sources
PubMed2006

In vitro tests to evaluate immunotoxicity: a preliminary study.

The implementation of Registration, Evaluation and Authorisation of new and existing Chemicals (REACH) will increase the number of laboratory animals used, if alternative methods will not be available. In the meantime, REACH promotes the use of in vitro tests and, therefore, a set of appropriated alternative testing methods and assessment strategies are needed. The immune system can be a target for many chemicals including environmental contaminants and drugs with potential adverse effects on human health. The aim of this study was to evaluate the predictivity of a set of in vitro assays to detect immunosuppression. The tests have been performed on human, rat and murine cells. Different endpoints have been assessed: cytotoxicity, cytokine release, myelotoxicity and mitogen responsiveness. For each of these endpoints IC50s values have been calculated. Six chemical substances, representative of the full range of in vivo responses and for which good human and/or animal data are available either from databases or literature, have been selected: two chemicals classified as not immunotoxic (Urethane and Furosemide), and four (tributyltin chloride (TBTC), Verapamil, Cyclosporin A, Benzo(a)pyrene) with different effect on immune system. All the tests confirmed the strong immunotoxic effect of TBTC as well as they confirmed the negative controls. For one chemical (Verapamil) the IC50 is similar through the different tests. The IC50s obtained with the other chemicals depend on the endpoints and on the animal species. The clonogenic test (CFU-GM) and the mitogen responsiveness showed similar IC50s between human and rodent cells except for Cyclosporin A and TBTC. All different tests classified the compounds analyzed in the same way.

Animals↗
PubMed2005

Primary chemotherapy with gemcitabine, epirubicin and taxol (GET) in operable breast cancer: a phase II study.

This trial was conducted to assess the activity and tolerability of the gemcitabine, epirubicin, taxol triplet combination in patients with operable breast cancer. After core biopsy, 43 women with stage II-IIIA breast cancer were treated with gemcitabine 1000 mg m(-2) over 30 min on days 1 and 4, epirubicin 90 mg m(-2) as an intravenous bolus on day 1, and taxol 175 mg m(-2) as a 3-h infusion on day 1, every 21 days for four cycles. The primary end point was the percentage of pathological complete responses (pCR) in the breast; secondary end points were tolerability, clinical response rates, overall and progression-free survival, tumour biomarkers before and after primary chemotherapy (PCT). All patients were included in safety and survival analyses; 41 eligible patients were evaluated for response. The overall clinical response rate was 87.8% (95% CI 77.8-97.8), with 26.8% complete responses (95% CI 13.3-40.3). A pCR in the breast was observed in six patients (14.6%; 95% CI 3.8-25.4); 15 patients (36.6%; 95% CI 21.9-51.3) had negative axillary lymph nodes. Grade 4 neutropenia was observed in 67.4% of the patients; febrile neutropenia occurred in 1.9% of cycles (granulocyte colony-stimulating factor was used in 3.2% of the cycles to shorten the duration of neutropenia). A statistically significant difference between Mib-1 at baseline (> or =20% in 71.4% of the patients) and at definitive surgery (28.6%, P < 0.05) was observed. The gemcitabine, epirubicin, taxol regimen is active and well tolerated as PCT for operable breast cancer. This combination allows the administration of full doses of active agents with a low incidence of febrile neutropenia.

Adult↗
PubMed2005

Locoregional anesthesia and coagulation.

The introduction of low molecolar weith heparin (LMWE) and the strong antithromboembolic prophylaxis protocols used in the USA, underlined the risk of spinal hemorrhage in patients receveing a neuraxial blockade. On the other side, the efficacy of these techniques over general anesthesia doesn't allow the anesthesist to miss this pratice, where possible. So it's necessary to quantify the spinal hematoma risk in patients assuming these drugs. Unfortunately, routine investigations on coagulation factors and platelets count are not reliable if patients are receiving LMWE. Waiting for dynamic tests concerning the coagulative status such as thromboelastography (TEG), many hospitals follow many different guidelines. For these reasons peripherical nerve block techniques are a good alternative, since they are not influenced by the efficacy of the coagulation system.

Anesthesia, Conduction↗
PubMed2004

Activity of first-line epirubicin and paclitaxel in metastatic breast cancer is independent of type of adjuvant therapy.

To evaluate the impact of prior adjuvant chemotherapy on response rate (RR), progression-free (PFS) and overall survival (OS) of metastatic breast cancer patients treated with epirubicin/paclitaxel (ET) regimens. In all, 291 patients enrolled in five studies in metastatic breast cancer were analysed: 101 (35%) were chemonaive, 109 (37%) had received adjuvant CMF and 81 (28%) adjuvant anthracyclines. Response rate to ET was 66%. Response rate was 63% for cyclophosphamide plus methotrexate plus 5-fluorouracil (CMF), 67% for prior anthracyclines and 68% in chemonaive patients (P=0.5). By multivariate analysis, adjusted odds ratio for response was 0.81 (95% CI: 0.37-1.79) for CMF and 0.92 (95% CI 0.43-2.01) for anthracyclines (P=0.86). The CR rates were 14% for both CMF and anthracyclines and 22% for chemonaive patients (P=0.2). By multivariate analysis, the relative odds of CR for CMF or anthracyclines were 0.40 and 0.39 as compared to chemonaive patients (P=0.036). The median PFS was 11.0 months for prior CMF, 10.2 months for anthracyclines and 12.5 months in chemonaive patients (P=0.33). In multivariate Cox's model, a nonsignificant increase in the risk of progression was seen in patients treated with adjuvant CMF or anthracyclines. The median OS was 23.8 months for CMF, 20.2 months for anthracyclines and 27.5 months in chemonaive patients (P=0.61). The same, nonsignificant, association was seen in multivariate analysis. The ET regimens provide satisfactory results in metastatic breast cancer, regardless of previous adjuvant chemotherapy.

Aged↗
PubMed2004

Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer.

In this phase II, multicentre trial, patients with metastatic breast cancer (MBC) were treated with a combination of gemcitabine, epirubicin and paclitaxel (GET). The primary objective of this study was to determine the tolerability and activity in terms of complete responce (CR) and overall response rate of the GET combination in this patient population. Patients with no prior treatment for MBC, and at least one bidimensionally measurable lesion received gemcitabine 1000 mg m(-2) intravenously (i.v.) over 30 min on days 1 and 4, followed by epirubicin i.v. at 90 mg m(-2) on day 1, and paclitaxel 175 mg m(-2) over 3 h on day 1, every 21 days, up to eight courses. From May 1999 to June 2000, 48 patients were enrolled from seven Italian institutions. A total of 297 chemotherapy courses were administered with a median of six cycles patient(-1) (range 1-8). Seven patients (15%) obtained CR and 27 patients (56%) had partial responce, for an overall response rate of 71% (95% CI: 58.3-83.7). After a median follow-up of 23.7 months (range 7.0-34.4), median progression-free survival was 10.5 months (95% CI: 9.2-11.7), and median overall survival 25.9 months. The main haematological toxicity consisted of grade 3 or 4 neutropenia that occurred in 62% of cycles (22% grade 4 and 40% grade 3). The GET combination is active and well tolerated as first-line chemotherapy for MBC.

Adult↗
PubMed2004

HER2 overexpression as a prognostic factor in metastatic breast cancer patients treated with high-dose chemotherapy and autologous stem cell support.

We retrospectively evaluated the predictive and prognostic role of HER2 expression in 44 metastatic breast cancer (MBC) patients treated with high-dose consolidation chemotherapy (HDCT) and autologous stem cell support after induction chemotherapy (IC) with six courses of epirubicin+paclitaxel (22 patients) or gemcitabine+epirubicin+paclitaxel (22 patients). HER2 expression was evaluated by an immunohistochemical method (Herceptest, Dako). A total of 13 patients (29.5%) showed a HER2 overexpression (score 3+). After IC, nine patients were in complete response (CR), 30 in partial response (PR), and five in stable disease (SD); after HDCT, 20 (45.5%) obtained a CR, and 23 were in PR, for a conversion rate of 48.5%. Conversion rate for HER2-positive patients was 87.5 vs 37% for HER2-negative patients (P=0.018). The median progression-free (PFS) and overall survivals (OS) were 17.6 (95% CI 13.2-22.0) and 44 (95% CI 25.9-62.3) months, respectively. Patients with HER2 overexpression experienced a significantly (P=0.0042) shorter median PFS (15.3 months, 95% CI 11.1-19.5) compared to HER2-negative patients (21.3 months, 95% CI 14.3-28.4). The median OS was 27.6 months (95% CI 4.5-50.7) in HER2-positive patients and 50.3 months (95% CI 38.7-62.0) in HER2-negative patients (P=0.345). These results indicate that HER2 overexpression predicts a worse outcome for patients with MBC treated with HDCT, despite the high CR rate obtained in this subset of patients.

Adult↗
PubMed2002

Gemcitabine, epirubicin and paclitaxel: pharmacokinetic and pharmacodynamic interactions in advanced breast cancer.

BACKGROUND: The objectives of this study were to investigate the disposition of gemcitabine, epirubicin, paclitaxel, 2',2'-difluorodeoxyuridine and epirubicinol, and characterize the pharmacokinetic and pharmacodynamic profile of treatment in patients with breast cancer. PATIENTS AND METHODS: The drug dispostion in 15 patients who received gemcitabine 1000 mg/m2, epirubicin 90 mg/m2 and paclitaxel 175 mg/m2 (GEP) on day 1 of a 21-day cycle, was compared with that of patients treated with epirubicin 90 mg/m2 and paclitaxel 175 mg/m2 (EP, n = 6) and epirubicin 90 mg/m2 alone (n = 6). Drug and metabolite levels in plasma and urine were assessed by high-performance liquid chromatography and parameters of drug exposure were related to hematological toxicity by a sigmoid-maximum effect (Emax) model. RESULTS: Paclitaxel administration significantly increased the epirubicinol area under the concentration-time curve, from 357+/-146 (epirubicin) to 603+/-107 (EP) and 640+/-81 h x ng/ml (GEP), and reduced the renal clearance of epirubicin and epirubicinol by 38 and 52.2% and 34.5 and 53% in GEP- and EP-treated patients, respectively, compared with epirubicin alone. Gemcitabine had no apparent effect on paclitaxel and epirubicin pharmacokinetics, and renal clearance of epirubicin and epirubicinol. The only pharmacokinetic/pharmacodynamic relationship observed was between neutropenia and the time spent above the threshold plasma level of 0.1 micromol/l (tC0.1) of paclitaxel, with the time required to obtain a 50% decrease in neutrophil count (Et50) of GEP being 7.8 h, similar to that of EP. CONCLUSIONS: Paclitaxel and/or its vehicle, Cremophor EL, interferes with the disposition and renal excretion of epirubicin and epirubicinol; gemcitabine has no affect on epirubicin and paclitaxel plasma pharmacokinetics and renal excretion of epirubicin, while neutropenia is not enhanced by gemcitabine.

Adult↗
PubMed2001

Gemcitabine, epirubicin, and paclitaxel combinations in advanced breast cancer.

Strategies to improve outcome in metastatic breast cancer include the first-line use of combinations of optimal doses of active agents, with the goal being to improve complete response rates and thus long-term survival. Although prior studies of anthracycline/taxane combinations generally have shown improved response rates and progression-free survival in comparison with single-agent regimens or anthracycline/cyclophosphamide-containing combinations, the data have not consistently demonstrated improved overall survival; indeed, they have yielded generally disappointing complete response rates. We evaluated the combination of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), epirubicin, and paclitaxel (GET) based on the hypothesis that epirubicin/paclitaxel is best suited for achieving delivery of optimal doses, and the addition of gemcitabine (which exhibits good single-agent activity with a favorable toxicity profile) will increase activity. In a phase II trial of 36 patients, the GET regimen produced reasonable toxicity and was associated with a 92% response rate, including complete responses in 31% of patients. The overall response rate increased to 97%, including complete responses in 41% of patients, with high-dose consolidation chemotherapy in 25 patients. A trial comparing GET with epirubicin/paclitaxel as first-line treatment in more than 600 patients with metastatic breast cancer has been initiated, with survival as the primary end point. Another large-scale trial is being planned to compare the GET regimen with an anthracycline/cyclophosphamide/paclitaxel combination in patients with early stage high-risk breast cancer. Semin Oncol 28 (suppl 7):15-17.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Gemcitabine plus epirubicin plus taxol (GET) in advanced breast cancer: a phase II study.

PURPOSE: To investigate the activity of the combination of gemcitabine (G) plus epirubicin (E) and taxol (T), (GET), in metastatic breast cancer, to evaluate the feasibility of this regimen as induction before high dose chemotherapy and to study the pharmacokinetic interactions of these three drugs. PATIENTS AND METHODS: Metastatic breast cancer patients, with bidimensionally measurable disease were eligible. Treatment consisted of G 1000 mg/sqm days 1 and 4 plus E 90 mg/sqm day 1 plus T 175 mg/sqm/3 h day 1, every 21 days. After six courses of GET, patients aged less than 60 years, in complete or partial remission or stable disease entered a programme of high dose chemotherapy (HDCT), as consolidation treatment. RESULTS: Thirtysix patients were included in this study. Grade 4 neutropenia was observed in 64% of the patients, with four episodes of febrile neutropenia; 39% of the patients experienced mild to moderate peripheral neuropathy; grade 2 and 3 mucositis occurred respectively in 9 (25%) and 6 (17%) patients. The overall response rate to GET was 92% (95% CI, 77.53%-98.25%); CR 31% and PR 61%. After six courses of GET, 25 patients received HDCT, leading to an overall response rate of 96% with 58% CR. At a median follow up of 25 months (range 8-39), 13 out of 36 patients are progression free and 26 alive. Median progression free survival is 21 months, while median overall survival has not yet been reached. The pharmacokinetic data show that G does not influence the interactions between E and T, while gemcitabine kinetics remains unchanged. CONCLUSIONS: The results of the present study indicate that the addition of G to E plus T as front line treatment for advanced breast cancer is well tolerated with an ORR of 92%. On the basis of the high activity and interesting progression free and overall survival rates, the GET combination deserves further evaluation in randomized trials.

Adult↗
PubMed2001

The gemcitabine/epirubicin/paclitaxel trials in advanced breast cancer.

Numerous trials have shown that the pharmacokinetic interferences of epirubicin (Ellence)/paclitaxel (Taxol) combinations produce less pharmacodynamic effect than doxorubicin/paclitaxel regimens. Paclitaxel is more easily combined when infused over 3 (as compared to 24) hours; the administration of optimal doses of both agents is important. Based on these findings, a phase II study was performed to evaluate the feasibility and activity of the combination of gemcitabine (Gemzar), epirubicin, and paclitaxel as first-line therapy in advanced breast cancer. Patients received gemcitabine at 1,000 mg/m2 on days 1 and 4, plus epirubicin at 90 mg/m2 on day 1, plus paclitaxel at 175 mg/m2/d on day 1 every 21 days. After six courses, patients less than 60 years old and in complete or partial remission or stable disease were treated with high-dose chemotherapy as consolidation treatment. The overall response rate was 92%, with 31% complete responses; 25 patients received high-dose chemotherapy, achieving a final overall response rate of 97%, with 47% complete responses. At a median follow-up of 25 months, median progression-free survival is 21 months. Grade 4 neutropenia was observed in 64% of patients. Other hematologic toxicities were mild. Mild to moderate peripheral neuropathy was experienced by 39% of patients; grade 2 or 3 mucositis occurred in 25% and 17% of patients, respectively. Based on these results, a multicenter trial has been started in seven Italian centers to confirm the feasibility of this regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Epirubicin/taxane combinations in breast cancer: experience from several Italian trials.

Doxorubicin/paclitaxel (Taxol) combinations are very active in advanced breast cancer, with objective response rates up to 90%, but have shown a high incidence of cardiotoxicity. A phase I/II trial replacing doxorubicin with epirubicin (Ellence), a less cardiotoxic analog, produced an objective response rate of 84%, but with a low rate of cardiotoxicity. A careful cardiac monitoring in more than 100 patients treated with this combination has demonstrated that the risk of congestive heart failure is below 10% up to a cumulative epirubicin dose of 990 mg/m2. To examine the possibility that the pharmacokinetic and pharmacodynamic interactions that occur when anthracycline and paclitaxel are administered together might result in subadditive antitumor activity, a phase III study is comparing concomitant vs sequential administration of epirubicin and paclitaxel in patients with advanced breast cancer. A phase I/II study of epirubicin plus docetaxel as first-line chemotherapy for advanced breast cancer patients evaluated the maximum tolerated doses and for subsequent studies recommended epirubicin at 75 mg/m2 plus docetaxel at 80 mg/m2. In the adjuvant setting, an ongoing phase III trial is comparing epirubicin plus paclitaxel vs FEC (fluorouracil, epirubicin, and cyclophosphamide [Cytoxan, Neosar]) in node-positive patients. Preliminary data confirm the cardiac safety of these treatments.

Breast Neoplasms↗
PubMed2001

New combinations with epirubicin in advanced breast cancer.

Several trials have shown that anthracyclines and taxanes can be combined to achieve response rates ranging from 70% to 90%, with complete responses ranging from 19% to 41%. In an attempt to increase the activity while maintaining tolerability, gemcitabine (Gemzar) was added to the epirubicin (Ellence)/paclitaxel (Taxol) regimen. Among 36 metastatic breast cancer patients treated with this new combination, the overall response rate was 92%, including 31% with a complete response. Another attempt to improve the outcome of metastatic breast cancer patients involves a phase III multicentric randomized trial (MANTA-1) to evaluate if paclitaxel maintenance therapy after anthracycline/taxane combination therapy can improve time to progression and overall survival. Although anthracyclines are more frequently used in the adjuvant setting, it is important for the clinicians to know whether this class of drugs can be used again for those patients who develop metastatic disease. An analysis of 312 patients treated with epirubicin containing regimens as first-line treatment for metastatic disease shows that epirubicin-based regimens are active in patients already exposed to anthracyclines in the adjuvant setting, and that the risk of cardiac toxicity is low up to a cumulative epirubicin dose of 990 mg/m2.

Adult↗
PubMed2000

Organotins induce apoptosis by disturbance of [Ca(2+)](i) and mitochondrial activity, causing oxidative stress and activation of caspases in rat thymocytes.

Di-n-butyltin dichloride (DBTC) and tri-n-butyltin chloride (TBTC) cause thymus atrophy in rodents. At low doses, antiproliferative modes of action have been shown to be involved, whereas at higher doses apoptosis seems to be the mechanism of thymotoxicity by these chemicals. In vitro, a similar concentration-dependency has been observed. The purpose of the present research was to investigate the mechanisms underlying DNA fragmentation induced by these organotin compounds in freshly isolated rat thymocytes. As previously shown for TBTC, DBTC is also able to significantly increase intracellular Ca(2+) level ([Ca(2+)](i)). The rise in [Ca(2+)](i), already evident 5 min after treatment, was followed by a dose- and time-dependent generation of reactive oxygen species (ROS) at the mitochondrial level. Simultaneously, organotins induced the release of cytochrome c from the mitochondrial membrane into the cytosol. ROS production and the release of cytochrome c were reduced by BAPTA, an intracellular Ca(2+) chelator, or rotenone, an inhibitor of the electron entry from complex I to ubiquinone, indicating the important role of Ca(2+) and mitochondria during these early intracellular events. Furthermore, we demonstrated that rotenone prevents apoptosis induced by 3 microM DBTC or TBTC and, in addition, that both BAPTA and Z-DEVD FMK (mainly a caspase-3 inhibitor) decreased apoptosis by DBTC (already shown for TBTC). Taken together these data show the apoptotic pathway followed by organotin compounds starts with an increase of [Ca(2+)](i), then continues with release of ROS and cytochrome c from mitochondria, activation of caspases, and finally results in DNA fragmentation.

Animals↗
PubMed2000

Role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early assessment of response to chemotherapy in metastatic breast cancer patients.

We investigated the role of 2-[18F]-fluorodeoxyglucose (FDG) positron emission tomography (PET) in the early evaluation of response to chemotherapy in metastatic breast cancer patients. Breast cancer patients who received an epirubicin/paclitaxel--containing regimen as first-line treatment for metastatic disease were included in this study. A PET study was performed within 1 week before the start of treatment, at day 8 after the first course, and at the end of the planned program of chemotherapy. Tumor response was determined clinically and radiographically every 2 courses of treatment. Thirteen patients with metastatic breast cancer who were referred for treatment protocols with gemcitabine/epirubicin/paclitaxel or epirubicin/paclitaxel chemotherapy regimens were included in this study. All metastatic sites were easily visualized on the baseline FDG-PET images, obtained 50 to 60 minutes after tracer injection. Nine patients who completed the planned courses of chemotherapy and the FDG-PET studies were available for analysis. In the six patients who achieved a response to treatment, median glucose standard uptake value (SUV) (semiquantitative analysis) was 7.65 (range, 3.4-12.3) at baseline, 5.7 (range, 2.8-7.6) at day 8 after the first course, and 1.2 (range, 0.99-1.3) at the end of the 6 planned courses of chemotherapy. Three patients who obtained a stable disease as best response had no significant decrease in tumor glucose SUV compared to baseline levels. Qualitative visual analysis in the six responding patients showed a decrease in delineation of tumor mass from background activity soon after the first course, while the nonresponding patients had no significant modification from basal levels. Semiquantitative FDG-PET scanning of metastatic breast cancer sites showed a rapid and significant decrease in tumor glucose metabolism soon after the first course of treatment in patients who achieved a response to first-line chemotherapy. On the contrary, no significant decrease was observed in nonresponding patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Role of epirubicin in advanced breast cancer.

Anthracyclines were first introduced for the treatment of metastatic breast cancer in the 1970s and are still among the most active single agents for the treatment of this disease. Unfortunately, their clinical value is limited by late-onset ventricular dysfunction. Epirubicin, an anthracycline analogue, does not eliminate the risk of cardiotoxicity but is less cardiotoxic and myelotoxic than doxorubicin at equimolar doses, thereby allowing the safe administration of cumulative doses between 950 and 1000 mg/m2. The inclusion of epirubicin in combination regimens, such as fluorouracil/epirubicin/cyclophosphamide (FEC), has been shown to be safe and active as first-line treatment for metastatic breast cancer. In the past few years, new drugs, including taxanes, have shown a high level of activity as single agents in the treatment of advanced breast cancer. Doxorubicin/paclitaxel combinations have shown high overall response rates (90%) as first-line chemotherapy of advanced breast cancer; however, congestive heart failure has been reported in up to 20% of patients. Epirubicin/paclitaxel combinations have been associated with grade 3 cardiotoxicity (6%) in only one study. We report findings of a trial of combination epirubicin/paclitaxel as first-line treatment of advanced breast cancer, with overall response rates (ORRs) of 84% and a complete response (CR) rate of 19%. Achieving a CR to first-line chemotherapy for advanced breast cancer appears to predict survival, and adding an active drug with a different mechanism of action and nonoverlapping toxicity might increase the percentage of CRs. We therefore tested the feasibility and activity of 6 to 8 courses of first-line treatment with a three-drug combination (gemcitabine 1000 mg/m2 days 1 and 4, epirubicin 90 mg/m2 day 1, and paclitaxel 175 mg/ m2 over 3 hours on day 1) in a phase II study of 36 metastatic breast cancer patients. Treatment was well tolerated, with an ORR of 92% (95% confidence interval: 77.53%-98.25%) and a CR of 31%. In considering retreating patients who progress or relapse after receiving an anthracycline-/taxane-containing regimen with the same active drugs, epirubicin appears ideal in both the adjuvant and metastatic breast cancer settings.

Antibiotics, Antineoplastic↗
PubMed2000

The gemcitabine/epirubicin/paclitaxel combination in advanced breast cancer.

The purpose of this study was to determine the response rate of the gemcitabine/epirubicin/paclitaxel combination (GET) and its feasibility as induction chemotherapy before high-dose consolidation treatment in patients with metastatic breast cancer. Patients received gemcitabine 1,000 mg/m2 on days I and 4, epirubicin 90 mg/m2 on day 1, and paclitaxel 175 mg/m2 on day I every 3 weeks for up to eight courses. After six courses of GET, responding patients or those with stable disease entered a high-dose chemotherapy program. All 36 enrolled patients were evaluated for toxicity and response. The GET combination was well tolerated, with myelosuppression the being most common toxicity; grade 4 neutropenia was reported in 56% of patients. The overall response rate was 89% (95% confidence interval, 73.4% to 96.9%), with a 28% complete response rate. The high-dose chemotherapy program resulted in a response rate of 92% and a complete response rate of 44%. As a result of the promising activity demonstrated in this phase II study with GET and following high-dose chemotherapy, three related studies are planned: an in vitro study evaluating the possible synergism of paclitaxel and gemcitabine, a phase III study comparing GET with epirubicin/paclitaxel in metastatic breast cancer, and a phase II trial evaluating GET in patients with operable breast cancer.

Adult↗
PubMed1999

Chemotherapy of non-small-cell lung cancer: role of erythropoietin in the management of anemia.

Main mechanisms involved in the development of chemotherapy-induced anemia are the direct bone marrow damage and the renal impairment with a secondary deficient production of erythropoietin. The first mechanism is induced by almost all cytotoxic drugs whilst the second one has been demonstrated with cisplatin treatment. NSCLC patients are generally treated with platinum-based chemotherapy and then both mechanisms are involved in the development of anemia which can be, as a consequence, more frequent and more severe compared to other cancer patients. Chemotherapy regimens such as MVP (mitomycin, vindesine, platin), cisplatin-etoposide and cisplatin-teniposide induce grade > or = 2 anemia in 64%, 46% and 83% of patients, respectively, with grade 3-4 anemia occurring in 29%, 15% and 24% of patients. New chemotherapy regimens are also associated with a high incidence of anemia. Carboplatin-paclitaxel induces grade 3-4 anemia in 34% of patients and 30% of patients need blood transfusions. Similarly, 33% of patients treated with cisplatin-gemcitabine require blood transfusions. Erythropoietin is able to correct anemia in nearly 60%-80% of patients receiving platinum-based chemotherapy and in nearly 40% of patients treated with regimens without platinum compounds, leading to a reduction in blood transfusion requirement. Moreover, erythropoietin is able to prevent anemia development in cancer patients. Due to the high incidence of anemia, erythropoietin may represent an important tool in the supportive care of NSCLC patients. Erythropoietin use is mainly limited by the economic cost and then efforts should be made to identify the subset of patients in whom this supportive therapy is cost-effective. Patient and disease characteristics, factors predicting the probability to be transfused as well as factors predicting the response to erythropoietin can be useful in selecting patients likely to benefit from erythropoietin therapy.

Anemia↗