[Show abstract][Hide abstract] ABSTRACT: Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor’s (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decrease overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct sutypes, with dissimilar clinical behaviour and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the “standard” treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets.
Full-text · Article · Dec 2014 · Cancer Treatment Reviews
[Show abstract][Hide abstract] ABSTRACT: Purpose: Chemotherapy regimens containing anthracyclines and taxanes represent the landmark of neoadjuvant systemic therapy of breast cancer. In advanced breast cancer patients liposomal anthracyclines (LA) have shown similar efficacy and less cardiac toxicity when compared to conventional anthracyclines. We performed this retrospective analysis in order to evaluate the efficacy and tolerability of neoadjuvant regimens including LA outside of clinical trials in routine clinical practice.
Methods: Fifty operable or locally advanced, HER2 negative, breast cancer patients were retrospectively identified in 5 Italian cancer centres. Nineteen patients had received 4 cycles of non-pegylated liposomal doxorubicin (NPLD) and cyclophosphamide, followed by 4 cycles of docetaxel, every 3 weeks. In 25 patients the reverse sequence was employed, and a third subgroup of 6 patients received 4 cycles of NPLD/cyclophosphamide every 3 weeks followed by 4 cycles of weekly carboplatin and paclitaxel.
Results: We observed 10 pathological complete responses (pCR) (20.0%, 95%CI, 9% to 31%), and 35 (70%, 95%CI, 57.3% to 82.7%) partial responses (pPR), whereas no patients progressed onto therapy. In the small subset of triple negative tumors the pCR rate was 37.5%, and in tumors expressing ER and/or PgR it was 16.7%. A pCR rate of 26.5% was observed in tumors with high Ki-67, whereas in tumors with low Ki-67 only one (6.2%) pCR was observed (p=0.14). Treatments were well tolerated. The most common toxicities were myelosuppression and palmar-plantar erytrodysesthesia; 4 asymptomatic and transient LVEF decrease have been recorded, without any case of clinical cardiotoxicity.
Conclusions: NPLD-cyclophosphamide and taxanes sequential regimens were proven effective and well tolerated in breast cancer patients with contra-indication to conventional anthracyclines undergoing neoadjuvant chemotherapy, even outside of clinical trials in everyday clinical practice.
Full-text · Article · Apr 2014 · Journal of Cancer
[Show abstract][Hide abstract] ABSTRACT: Although not life-threatening, vasomotor symptoms might have a detrimental effect on quality of life and represent a major determinant of poor therapeutic compliance in breast cancer patients. Limitations of hormonal therapies have fostered the use of non-estrogenic pharmacological agents, which mainly include centrally acting compounds, antidepressant drugs, serotonin-norepinephrine reuptake inhibitors and serotonin reuptake inhibitors. Integrating therapeutic tools have recently come from a wide range of heterogeneous approaches varying from phytoestrogens use to ganglion block. We herein critically review the most updated evidence on the available treatment options for management of vasomotor symptoms. The need for a patient-oriented approach following systematic evaluation of the presence and degree of vasomotor disturbances is also discussed and future perspectives in therapeutics are summarized.
No preview · Article · Dec 2013 · Expert Review of Anti-infective Therapy
[Show abstract][Hide abstract] ABSTRACT: Paclitaxel (PACL) plus gemcitabine (GEM) is an effective regimen for advanced breast cancer patients pretreated with anthracyclines. A prolonged GEM infusion at a fixed dose rate (FDR) of 10 mg/m²/min produces higher levels of intracellular active metabolites of GEM when compared with a standard 30-min infusion. In the present phase I/II trial, we investigated the association of FDR GEM plus PACL.
1,200 mg/m² was the dose of GEM recommended for the phase II study, in which patients received PACL at 150 mg/m², followed by FDR GEM at 1,200 mg/m² (total GEM infusion time = 120 min), both drugs administered biweekly.
Forty-two anthracycline-pretreated advanced breast cancer patients with disease recurrence following at least one line of chemotherapy were enrolled. Two (4.8%) and 12 (33.3%) patients experienced a complete and partial response, respectively, for an overall response rate of 38.1% (95% CI 23.4-52.8%). Median progression free survival and overall survival were 5 and 19.9 months, respectively. No statistically significant association was noted between in situ protein expression of RRM1 and BRCA1 (as assessed by immunofluorescence combined with automated quantitative analysis) and response to treatment in 15 patients with tissue available for analysis. Toxicity was mostly mild to moderate, mainly consisting of G3-G4 neutropenia (9.6%) and hypertransaminasemia (9.5%).
Biweekly FDR GEM in combination with PACL is an active and safe regimen for advanced breast cancer patients pretreated with anthracyclines. A prolonged infusion regimen of GEM does not seem to improve the efficacy of a standard 30-min infusion.
Full-text · Article · Mar 2011 · Cancer Chemotherapy and Pharmacology
[Show abstract][Hide abstract] ABSTRACT: Adjuvant treatment of early breast cancer has changed considerably in recent years, and the majority of patients are currently treated with the most active single agents in this setting. As a result, the decisions regarding the treatment of patients with metastatic breast cancer have become more difficult. In patients who have not received chemotherapy for early-stage breast cancer or were treated with CMF, many choices are available, including regimens containing anthracyclines or taxanes. Patients who received anthracyclines in the adjuvant setting, may sometimes be re-treated with these agents, and the inclusion of a taxane is frequently the most reasonable choice. Among taxanes, docetaxel should be preferred because it is the most active single agent, and has a synergistic action with several other drugs, when used in combination. Taxanes can be used also in selected patients who had received these agents as adjuvant treatment. In particular, docetaxel did not show complete cross-resistance with paclitaxel, whereas weekly paclitaxel is only minimally effective in patients resistant to docetaxel. Retreatment with trastuzumab combined with chemotherapeutic agents might be a reasonable option in patients who had received adjuvant chemotherapy with trastuzumab. Nevertheless, another recent option is the combination of chemotherapy with lapatinib. Currently, novel target agents are being developed, with the potential to improve survival in patients with metastatic breast cancer. Arguably, the future for treatment of these patients appears to be the combination of effective single agents, such as docetaxel, with novel biologic therapies.
No preview · Article · Nov 2009 · La Clinica terapeutica
[Show abstract][Hide abstract] ABSTRACT: Adjuvant treatment in hormone-receptor positive, HER2-negative early breast cancer is controversial. Chemotherapy benefit in this subset of patients is generally small, and a wide variability exists among dif-ferent subgroups of patients, depending on various patient and tumor characteristics. To select subsets of patients who will really benefit from chemotherapy, one of the possible strategy is based on multigene expression analysis. This approach is providing deeper insights into the biological heterogeneity of breast cancer, allowing to further sub-divide hormone-receptor positive tumors into groups, with different clinical behavior and response to treatments. Among less expensive and better validated methods, high levels of Ki67, a routinely assessed immunohistochemical marker of cell proliferation, can suggest the use of chemotherapy in this subset of patients. Generally, regimen used should include a taxane. In fact, retrospective analyses of clinical trials suggest that anthracyclines may be less active in hormone-receptor positive HER2-negative patients, while several other trials and meta-analyses involving taxanes, showed a benefit in terms of risk of relapse and death reduction. Among taxanes, docetaxel should be preferred because of a better therapeutic index, and a higher activity in comparison to paclitaxel. At present, reliable and accurate evaluation of histopathological and immunohistochemical factors may allow the choice of omitting adjuvant chemotherapy in patients with low risk hormone receptor positive HER2-negative breast cancer. Uncertainty still exists about chemotherapy benefit for a substantial proportion of women of this subgroup. Nevertheless, the addition of taxanes, mainly docetaxel, to anthracyclines, seems to overcome the relative chemoresistance of hormone-receptor positive tumors, providing a benefit in disease free survival and overall survival.
No preview · Article · Nov 2009 · La Clinica terapeutica
[Show abstract][Hide abstract] ABSTRACT: Since the first use of chemotherapy, many efforts were devoted to develop drugs with a specific anticancer activity. Nevertheless, although several approaches to this end were used leading to significant results in cancer treatment, chemotherapy has mainly a palliative effect. The remarkable scientific advances in the knowledge of molecular changes in neoplastic diseases brought to development of new drugs with a specific molecular target. In some cases, this approach against a single molecular target, has been extremely successful, like imatinib in GIST. However, since in most cases tumor growth involves multiple genetic changes, it seems more appropriate to develop multitargeted agents. A successful way to improve target selectivity of anticancer drugs and to better choose patients to treat could be the use phase 0 clinical trials. In the future, the hope is to discover all genetic changes in each cancer patient and to restore the normal function of the cell with the aid of more advanced technologies.
No preview · Article · May 2008 · La Clinica terapeutica
[Show abstract][Hide abstract] ABSTRACT: To determine wether primary CEF is effective in locally advanced breast cancer, as measured by response, local recurrences, disease free survival (DFS) and overall survival (OS).
From 1990 to 1998, 62 patients with stage III disease were enrolled into a prospective study at Regina Elena Institute for Cancer Research, Rome. Inflammatory breast cancer (IBC) was included. Patients received three 21 days cycles of chemotherapy that consisted in epirubicin 50 mg/m2, cyclophosphamide 400 mg/m2, and fluorouracil 500 mg/m2 i.v. on days 1 and 8. G-CSF (300 microg) was given subcutaneously every other day from day 5 to day 17. After primary chemotherapy, whenever possible, mastectomy or conservative surgery was performed. Subsequently responding patients received the same regimen, while non responders were given a non cross resistant chemotherapy. In case of conservative surgery or initial T4 tumor radiation therapy was performed at the end of adjuvant chemotherapy. ER positive patients received tamoxifen 20 mg/d for five years.
Seven IIIA patients had a median OS of 43 months (C.I. 95%, 31-55) and DFS of 42 months (C.I. 95%, 16-68), while 15 IBC patients had a median OS of 52 months (C.I. 95%, 52-79) and DFS of 27 months (C.I. 95%, 14-39). Forty IIIB non inflammatory breast cancer patients had a median DFS of 87 months (C.I. 95%, 1-175); median OS was not reached. Ten-year OS was 28.6% for stage IIIA, 50.6% for stage IIIB and 36% for IBC.
Primary CEF appear to be an effective treatment. In our study we obtained a good local control and interesting long term data of disease free and overall survival.
No preview · Article · Jul 2007 · La Clinica terapeutica
[Show abstract][Hide abstract] ABSTRACT: Primary (neoadjuvant) systemic chemotherapy is the standard treatment for locally advanced breast cancer and a standard option for primary operable disease. Although survival results are similar, primary chemotherapy has the following advantages in comparison to adjuvant chemotherapy: it represents a chemosensitivity test in vivo and can be of value in determining the prognosis of the patient since pathologic complete responses are related to improved survival. Among a variety of primary chemotherapy regimens currently available, the most effective seem to be those containing both anthracyclines and taxanes, expecially when these agents are administered sequentially. There are also several ongoing studies evaluating primary hormonal therapy and the combination of cytotoxic chemotherapy and targeted agents. It is conceivable that in the future primary chemotherapy of breast cancer will be increasingly used. In fact, besides its clinical effectiveness, primary chemotherapy is extremely important to evaluate new agents and to find useful prognostic and predictive factors.
No preview · Article · Jan 2007 · La Clinica terapeutica
[Show abstract][Hide abstract] ABSTRACT: The treatment of refractory metastatic breast cancer is primarily palliative, without a significant impact on overall survival. Among the innovative combinations in this unfavourable setting, paclitaxel and gemcitabine showed a possible synergistic action and an encouraging activity in some clinical trials. This phase II study was carried out to evaluate paclitaxel-gemcitabine combination in very heavily pretreated advanced breast cancer on a bi-weekly schedule.Thirty-nine women with advanced breast cancer were treated with paclitaxel 150 mg/m2 as 3 hrs infusion, and gemcitabine 1,500 mg/m2 as 30 mins infusion, both drugs administered on days 1, 15, with cycles repeated every 28 days. All but two patients received granulocyte colony stimulating factor (G-CSF) on days 7 to 9 and 20 to 22 of every cycle. More than two third (71%) of the patients had previously received two or more chemotherapy regimens for advanced disease, including almost all active agents in this disease. Objective responses were observed in 18 out of 34 evaluable patients (53%; 95% CI, 36% to 70%). Disease remained stable in 7 patients (21%). Responses by sites were 67% in soft tissue and in bone, and 48% in visceral disease. Median time to progression and overall survival were 9 and 20 months, respectively. Treatment was well tolerated, with G3-4 neutropenia in 8%, and G 1-2 thrombocytopenia in 13% of the patients; non-hematological toxicities were mild, with G3 hepatotoxicity in 5% of the patients, and G3 peripheral neurotoxicity in 10% of the patients. Biweekly paclitaxel/gemcitabine combination with G-CSF support appears to be very active as salvage therapy in heavily pretreated breast cancer patients, with a very favourable safety profile.
Full-text · Article · Apr 2006 · Journal of experimental & clinical cancer research: CR
[Show abstract][Hide abstract] ABSTRACT: To evaluate the comparative efficacy of varying intensity schedules of recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) support in preventing febrile neutropenia in early breast cancer patients treated with relatively high-dose epirubicin plus cyclophosphamide (EC).
From October 1991 to April 1994, 506 stage I and II breast cancer patients were randomly assigned to receive, in a factorial 2 x 2 design, epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 intravenously on day 1 every 21 days for 4 cycles +/- lonidamine +/- G-CSF. The following five consecutive G-CSF schedules were tested every 100 randomly assigned patients: (1) 480 microg/d subcutaneously days 8 to 14; (2) 480 microg/d days 8, 10, 12, and 14; (3) 300 microg/d days 8 to 14; (4) 300 microg/d days 8, 10, 12, and 14; and (5) 300 microg/d days 8 and 12.
All of the G-CSF schedules covered the neutrophil nadir time. Schedule 5 was equivalent to the daily schedules (schedules 1 and 3) and to the alternate day schedules (schedules 2 and 4) with respect to incidence of grade 3 and 4 neutropenia (P = .79 and P = .89, respectively), rate of fever episodes (P = .84 and P = .77, respectively), incidence of neutropenic fever (P = .74 and P = .56, respectively), need of antibiotics (P = .77 and P = .88, respectively), and percentage of delayed cycles (P = .43 and P = .42, respectively). G-CSF had no significant impact on the delivered dose-intensity compared with the non-G-CSF arms.
In the adjuvant setting, the frequency of prophylactic G-CSF administration during EC could be curtailed to only two administrations (days 8 and 12) without altering outcome. This nonrandomized trial design provides support for evaluating alternative, less intense G-CSF schedules for women with early breast cancer.
Preview · Article · Nov 2005 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Controversies exist regarding the classification of the emetogenic potential of chemotherapeutic agents such as taxanes, gemcitabine and irinotecan and the antiemetic prophylaxis for acute emesis to be administered. Instead, no prophylaxis for delayed emesis has been suggested. A prospective, observational study was carried out in 103 Italian oncological centers to evaluate the prescriptions of antiemetics and the incidence of nausea and vomiting in patients submitted to these chemotherapy agents. Two hundred and nine patients treated with taxanes, 300 with gemcitabine and 93 with irinotecan were evaluated. For the prophylaxis of acute emesis a 5-HT3 antagonist alone or in combination with a corticosteroid was administered to 86.6% of patients receiving taxanes, to 59.3% of those receiving gemcitabine and to 96.8% of those submitted to irinotecan. 20% to 40% of patients received antiemetic prophylaxis for delayed emesis. In taxane-treated patients the incidence of acute vomiting and nausea was 6.2% and 27.3%, respectively, while in gemcitabine- and irinotecan-treated patients it was 6.0/33.4% and 17.9/58.9%, respectively. In conclusion, the study showed that almost all patients received prophylaxis for acute emesis and that there is overprescription of 5-HT3 antagonists. The incidence of acute emesis is low; therefore, randomized clinical trials are necessary to verify the utility of prophylaxis and to find the best antiemetic treatment.
[Show abstract][Hide abstract] ABSTRACT: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity.
From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients).
Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non-G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non-G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively).
EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.
No preview · Article · Oct 2003 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Breast cancer (BC) is the most common malignancy and the second most common cause of cancer-related death in Western European and North American women. Neoadjuvant chemotherapy may be used in the management of both BC patients with locally advanced disease, and those with earlier stage and operable tumors. Data from recently phase III trials and worldwide consensus conference document the benefit of adjuvant chemotherapy in improving disease free survival and overall survival for patients diagnosed with invasive BC > 1 cm. When BC cells metastasize to distant organs, the disease is incurable, but chemotherapy may offer these patients a significant palliation.
[Show abstract][Hide abstract] ABSTRACT: This phase II multicenter trial was aimed at investigating the activity of epirubicin-vinorelbine combination as first-line chemotherapy in metastatic breast cancer patients.
Ninety-seven patients with metastatic breast cancer and no prior exposure to anthracyclines received the following regimen: epirubicin 100 mg/m(2) by intravenous (IV) bolus infusion on day 1 plus vinorelbine 25 mg/m(2) by 30-minute IV infusion on days 1 and 5, every 3 weeks for up to eight cycles. All patients also received granulocyte colony-stimulating factor (G- CSF) on days 7 to 12 of every cycle.
Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 65 out of 92 assessable patients (70.6%; 95% CI, 62% to 80%). Disease remained stable in 17 patients (18.5%). Responses were observed in all disease sites, being 94% in soft tissue, 60% in bone, and 66% in visceral disease. Median time to response, median duration of response, median time to progression, and median overall survival were 2, 9, 10, and 26 months, respectively. The dose-limiting toxicity was neutropenia, which was grade 4 in 36% of the patients, and was accompanied by fever in 26% of the cases. Grade 3 to 4 mucositis was encountered in 28% of the patients. Other toxicities were mild to moderate. No cardiotoxicity was observed.
The epirubicin-vinorelbine combination with G-CSF support has been shown in this study to be highly active as first-line treatment of metastatic breast cancer patients, with significant although transient toxicity. This justifies further evaluation in the neoadjuvant setting and in early-stage breast cancer.
No preview · Article · Jul 2002 · Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Aims and Background. The necessity of an antiemetic prophylaxis in patients treated with chemotherapy of low emetogenic potential, such as 5-fluorouracil ± folinic acid fractionated over several consecutive days, is controversial. The aim of the study was to evaluate the therapeutic behavior of oncologists on this issue. Methods. All consecutive in and out patients who started chemotherapy in 33 Italian oncological departments from June 24 to July 6, 1996, were studied. The antiemetic prescription pattern and its effectiveness, in patients submitted to 5-fluorouracil ± folinic acid were evaluated. Results. Of the 1956 patients submitted to cancer chemotherapy, 259 patients received 5-fluorouracil ± folinic acid. Of these, 186 patients were treated for 5 consecutive days, 47 for 4 days, 20 for 3 days and 6 for 2 days. A total of 219 (84.5%) received an antiemetic prophylaxis: 43.4% a 5-HT3 antagonist ± steroids, 37.5% an antidopaminergic drug, 10.9% a steroid ± antidopaminergic drug, and 8.2% other drugs. Only 40 patients (15.5%) did not receive an antiemetic prophylaxis. Overall complete protection from vomiting/nausea was 225/259 (86.9%)/163/259 (62.9%). The complete protection from vomiting/nausea during the 5 days in the 186 patients was not significantly different among patients receiving or not an antiemetic prophylaxis (88.1%/64.9% vs 88.9%/55.6%). At unifactorial analysis, the previous experience of vomiting/nausea caused by chemotherapy was found to be a significant prognostic factor. In fact, overall complete protection from vomiting/nausea was significantly inferior in patients who had previous experience of vomiting/nausea (65.1%/35.0%) with respect to those who did not (91.2%/75.4%, P < 0.001/ > 0.001, respectively). Conclusions. The study showed that in clinical practice patients submitted to 5-fluorouracil ± folinic acid obtained a similar high protection from vomiting and nausea regardless of whether or not antiemetic prophylaxis was given. It would be therefore reasonable not to treat patients undergoing such chemotherapy, whereas patients with previous experience of vomiting/nausea caused by chemotherapy should be given an antiemetic prophylaxis.
[Show abstract][Hide abstract] ABSTRACT: The efficacy of CEA and CA15-3 tumor markers in monitoring breast cancer was evaluated in 1365 patients with either benign (n=534) or malignant (n=831) breast diseases. Thirty-nine breast cancer patients were monitored before and after neoadjuvant chemotherapy. Three hundred forty-nine patients were monitored during post-surgical follow-up for either a minimum of 5 years or until time of recurrence. Twenty-one patients with metastases were also monitored during chemotherapy. Elevated CA 15-3 and TPS levels were found in 28.6% and 30.0% of patients. CA 15-3 and TPS sensitivities rose to 71.9% and 66.3% in metastatic patients, respectively. The addition of TPS to CA 15-3 increased the sensitivity up to 44.4% in the overall population, and to 87.6% in patients with metastases. During post-surgical follow-up CA 15-3 was elevated in 65.7% and TPS in 61.3% of patients with recurrence. The combination of TPS and CA 15-3 increased the overall sensitivity by 12.7%. Longitudinal monitoring of metastatic patients undergoing chemotherapy demonstrated that, when positive, both CA 15-3 and TPS paralleled response to treatment. TPS monitoring may provide additional value when used in combination with CA15-3 during post-surgical follow-up of breast cancer patients.
No preview · Article · Jun 2001 · Breast Cancer Research and Treatment
[Show abstract][Hide abstract] ABSTRACT: To better determine docetaxel activity in patients with well-defined anthracycline-resistant breast cancer.
From October 1996, we carried out a phase II trial in 69 heavily pretreated patients with advanced breast cancer with docetaxel 100 mg/m(2) by a 1-hour infusion on day 1, with cycles repeated every 3 weeks. Patients were classified as having primary anthracycline resistance (n = 32), secondary anthracycline resistance (n = 7), anthracycline pretreatment (n = 22) or no anthracycline pretreatment (n = 8).
Among 68 evaluable patients, we observed 6 (9%) complete responses and 27 (40%) partial responses, for an overall response rate of 49% (95% confidence interval 37-61%); the disease remained stable in 17 patients (25%). Responses according to the above subgroups were as follows: primary anthracycline resistance 41%, secondary anthracycline resistance 43%, anthracycline pretreatment 64% and no anthracycline pretreatment 43%. The median time to response, median time to progression and median overall survival were 2, 7 and 10 months, respectively. Myelosuppression was the dose-limiting toxicity, with grade 4 neutropenia occurring in 47% of the patients and neutropenic fever in 12%. G-CSF was added in the case of grade 4 febrile neutropenia; a 25% reduction in the dose of docetaxel was required in 4 patients. Other side effects were mild.
The results of the present trial confirm the high activity of docetaxel in heavily pretreated patients with advanced breast cancer, including those with strictly defined anthracycline resistance.
[Show abstract][Hide abstract] ABSTRACT: Based on preclinical data showing a synergistic activity of simultaneous administration of vinorelbine and paclitaxel, we carried out a phase II trial in previously untreated advanced breast cancer patients. Treatment consisted of vinorelbine 25 mg/m(2) and paclitaxel 150 mg/m(2), both drugs given by intravenous infusion over 3 h on day 1, with cycles repeated every 3 weeks. Granulocyte colony-stimulating factor, 300 microg subcutaneously, was given on days 7-12 to the first 10 patients. From October 1995 to January 1997, 43 patients with advanced breast cancer entered the study, and 41 were evaluable for response. We obtained 2 complete responses (5%) and 18 partial responses (44%), for an overall response rate of 49% (95% CI 34-64%). Median time to response, time to progression and survival were 2, 7 and 22 months, respectively. Myelosuppression was the dose-limiting toxicity, with G4 neutropenia in 21% and neutropenic fever in 7% of the patients. Other toxicities were mild. Simultaneous infusion of vinorelbine and paclitaxel is a well-tolerated and active regimen in metastatic breast cancer, with overall results similar to those reported with more toxic regimens; furthermore, it may be a good option in patients with anthracycline contraindications.
[Show abstract][Hide abstract] ABSTRACT: To assess the activity and toxicity of gemcitabine in locally advanced or metastatic soft tissue sarcoma patients (pts).
Gemcitabine was administered on days 1, 8, 15 every 4 weeks at a dose of 1.000/1.250 mg/m2, respectively, in pretreated or not pretreated pts.
Eighteen pts entered this phase II trial; sixteen had been previously treated with anthracyclines and ifosfamide. A partial response was observed in a woman with fibrous malignant istocytoma, whereas in 7 pts the disease remained stable. Median time to progression was 4 months. The treatment was well tolerated. Grade 4 toxicity was not observed.
These results do not suggest that gemcitabine, in the dose and schedule used in this trial, may be of value in the treatment of soft tissue sarcomas.
No preview · Article · Jan 1999 · La Clinica terapeutica