Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies.

Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease.

Recurrence risk in small, node-negative, early breast cancer: a multicenter retrospective analysis.

PURPOSE: Recurrences and deaths are known to occur, even if less frequently, in small, node-negative breast cancer patients, and decision on adjuvant treatments remains controversial. In the present analysis, we evaluate recurrence risk in patients with pT1 a, b, c, node-negative, breast cancer, accordingly with some prognostic biological factors. METHODS: We retrospectively evaluated 900 node-negative patients (pT1a, b, c) surgery treated between 2000 and 2009 in four Italian oncologic centers. We defined 3 different cohorts: ER positive (ER+); Her-2 positive (Her-2+); and triple negative (TN). RESULTS: pT1a was seen in 7.6% of patients, 37.7 % pT1b, 54.8 % pT1c. Concerning the 3 different cohorts, 58.2 % were ER+; 10.8 % were Her-2+; 8.2 % were TN. Overall, chemotherapy was given to 3.0 %, 27.2 %, 69.8 % of pT1a, b, c, respectively, and to 22.7 %, 58.8 %, 68.9 % of ER+, Her-2+, TN subgroups. At a median follow-up of 67 months, 5-year DFS was 96.3 %, 89.2 %, 89.4 % in pT1a, b, c, respectively (100 %, 93.6 %, 89.8 % in ER+; 100 %, 78.7 %, 85.0 % in Her-2+; 100 %, 76.8 %, 85.2 % in TN) (p = ns). At multivariate analysis, histologic grade and Ki-67 resulted independent prognostic factors. Overall, 5-year OS was 98 %, without differences among pT1a, b, c, or among the 3 cohorts. CONCLUSIONS: Overall, 5-year DFS was very favorable in this series of small, node-negative breast cancers, but Her-2+ and TN cohorts have a higher recurrence rate than ER+ cohort (p < 0.0001); pT1c, but also pT1b, in Her-2+ and TN subgroups, have a worse outcome, and effective chemotherapy treatment should be considered in these unfavorable subgroups.

A multicenter phase III prospective randomized trial of high-dose epirubicin in combination with cyclophosphamide (EC) versus docetaxel followed by EC in node-positive breast cancer. GOIM (Gruppo Oncologico Italia Meridionale) 9902 study.

BACKGROUND: The Gruppo Oncologico Italia Meridionale 9902 trial compared four cycles of high-dose epirubicin plus cyclophosphamide (EC) with four cycles of docetaxel (Taxotere, D) followed by four cycles of EC as adjuvant treatment of node-positive breast cancer. PATIENTS AND METHODS: Patients were randomly assigned to EC (E 120 mg/m(2), C 600 mg/m(2), arm A) for four cycles or four cycles of D (100 mg/m(2)) followed by four cycles of EC (arm B), both regimens every 21 days. Hormone receptor-positive patients were given hormonal therapy for 5 years. Primary end point was 5-year disease-free survival (DFS). Secondary objectives were overall survival (OS) and safety. RESULTS: There were 750 patients enrolled. With a median follow-up of 64 months, 5-year DFS was 73.4% in both arms, and 5-year OS was 89.5% versus 90.7% in arm A and B [hazard ratio was 0.99 (95% confidence interval for DFS 0.75-1.31; P = 0.95)], respectively. Grade 3-4 toxicity was more common in arm B. CONCLUSIONS: This study did not show advantages from the addition of docetaxel to high-dose EC as adjuvant chemotherapy in node-positive breast cancer. The small sample size and low number of DFS events may have limited the ability to observe statistically significant difference between the two arms.

A multicenter phase II randomized trial of docetaxel/gemcitabine versus docetaxel/capecitabine as first-line treatment for advanced breast cancer: a Gruppo Oncologico Italia Meridionale study.

OBJECTIVE: To evaluate two docetaxel-based regimens as first-line treatment in advanced breast cancer patients. METHODS: Patients were randomly assigned to docetaxel/gemcitabine (arm A: docetaxel 75 mg/m(2) on day 1, gemcitabine 1,000 mg/m(2) on days 1 and 8) or docetaxel/capecitabine (arm B: docetaxel 75 mg/m(2) on day 1, capecitabine 1,250 mg/m(2) twice daily on days 1-14); both chemotherapy regimens were repeated every 21 days. The primary objective of the study was to evaluate the response rate. RESULTS: Seventy-two patients were enrolled (36 each in arms A and B). Responses according to intention-to-treat analysis were as follows: arm A, 41.7% [95% confidence interval (CI) 25.6-57.8]; arm B, 38.9% (95% CI 23-54.8). Median progression-free survival was 10.9 months (95% CI 8.1-13.7) in arm A and 10 months (95% CI 8.8-11.2) in arm B. Overall survival was 26 months (95% CI 22.0-30.0) in arm A and 28 months (95% CI 23.4-32.6) in arm B. Both treatments were well tolerated; myelosuppression was the dose-limiting toxicity, with grade 3-4 neutropenia in 13.8 and 19.4% of the patients in arms A and B, respectively. No relevant differences in other toxicities were observed in the two arms, except for diarrhea (13.9%) and hand-foot syndrome (11.1%), which occurred only in arm B. CONCLUSIONS: Both regimens were active and well tolerated in advanced breast cancer.

[Specificity of action of anticancer agents]. / Specificità d'azione dei farmaci antineoplastici.

Since the first cancer chemotherapy use, efforts have been made in identifying drugs with an antitumor specific action, but cancer is a very complex situation to be cured with a single agent, and to increase drugs selective cytotoxicity new agent combinations, or innovative cellular cycle related schedule, or the use of pro-drugs have been developed. Notwithstanding some relevant improvements in results, chemotherapy remains often a palliative approach. The improved knowledge of the biology of cancer, and of molecular mechanisms and specific targets, has recently modified the approach to various tumors. In particular, the identification of a single and specific genetic alteration in some tumors such as myeloid chronic leukaemia or gastrointestinal stromal tumors (GIST) led to the development of imatinib, a "target" drug with a multikinase inhibitor activity towards the specific genetic alteration; this unique opportunity is not applicable to other tumors, because usually tumors have multiple genetic alterations with very complex molecular pathways. The development of drugs with a multitarget action is probably the best approach to the majority of human cancers, but other possibility are the combination of multiple agents, each with known selective activity towards a specific molecular target, or the choice of a chemotherapic drug in combination with one or more molecularly targeted drugs. The knowledge of the multiple and extremely complex molecular pathways of the neoplastic cells will hopefully drive oncologic science towards a more "exact" science, with the use of "personalized" treatment in each cancer patient.

[Psyche and cancer]. / Psiche e cancro.

Although the relationship between psyche and cancer dates back many centuries, and several studies were conducted on this topic during the last decades, the role of psychological factors in the development of cancer is still controversial. Although a lot of factors have been considered, attention has been focused mainly on stress, which has been evaluated also in experimental models. Generally, the results of case-control studies have been contradictory, and at times more stressfull events have been recorded in patients with benign tumors than in those with cancer. On the contrary, a higher incidence of stress-related cancers has not been documented in cohort studies. Since cancer is a genetic disease, it is difficult to hypothesize that psychological factors may permanently alter nucleotide sequence giving rise to multiple mutations needed for cancer development. At present, there is no sufficient evidence to affirm that psychological factors may contribute without doubt to cancer development.

[Fiberoptic bronchoscopy as diagnostic tool in primitive lung cancer]. / Ruolo diagnostico della fi brobroncoscopia nelle neoplasie polmonari primitive.

OBJECTIVE: The aim of this study was to assess the diagnostic role of fiberoptic bronchoscopy in primitive lung cancers in relation to the sensibility, the specificity and the cost of the examination. MATERIALS AND METHODS: We analysed the diagnostic flow-charts of 473 patients with suspected primitive lung cancer consecutively examined during a period of 4 years (2003-2006). The results were analysed comparing patients observed in the period 2003-2004 with those observed during 2005-2006. The number and type of samples collected and the protocols utilized were considered. RESULTS: In overall patients the reliability of the fiberoptic bronchoscopy was 61.7%, with a significant increase from 47.5% in 2003-2004 to 74.4% in 2005-2006. An important role in improving the diagnostic relevance of the exam was assumed by the more frequent adoption of biopsies and trans-bronchial needle aspiration on parenchyma and mediastinal lymph nodes. CONCLUSIONS: The fiberoptic-bronchoscopy associated to advanced tissue sampling techniques represents the gold standard for the diagnosis of lung cancer, due to high sensitivity and specificity and moderate cost.

[Adjuvant chemotherapy in hormone-receptor positive HER2-negative early breast cancer]. / Chemioterapia adiuvante del carcinoma della mammella con recettori ormonali positivi HER2-negativo.

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.

[Role of adjuvant chemotherapy in the choice of chemotherapeutic treatment of metastatic breast cancer]. / Ruolo della chemioterapia adiuvante nella scelta del trattamento chemioterapico del carcinoma mammario metastatic

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.

[Development of docetaxel in the adjuvant chemotherapy of breast cancer]. / Sviluppo del docetaxel nella chemioterapia adiuvante del cancro della mammella.

The development of taxanes in cancer chemotherapy required several decades of research mainly because of the difficulty related to supply and formulation of paclitaxel. Lesser difficulty was encountered in the development of docetaxel, which initially took place in breast cancer. In this disease, docetaxel showed a significant activity, probably superior to that of paclitaxel. In the first-generation studies in patients with early breast cancer, comparing anthracycline-based regimens with regimens containing anthracyclines and taxanes, docetaxel significantly improved survival independently from schedule, either sequential or concurrent. The aim of current second-generation studies, comparing taxanes in all study arms, is to answer several questions, including the best administration schedule and the best taxane to be used. Currently, the use of docetaxel in the adjuvant chemotherapy of breast cancer represents one of the most important achievements in the treatment of this disease. However, since further improvement in therapeutic results are needed, it is likely that in the future docetaxel will be used in combination with molecular targeted agents.

[Target selectivity of anticancer drugs]. / Specifi cità d'azione dei farmaci antitumorali.

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.

Docetaxel in the adjuvant therapy of HER-2 positive breast cancer patients.

Considering the clinical benefit of trastuzumab in advanced breast cancer, fi ve prospective adjuvant randomized trials have recently been completed and early results have been published. Two of them, (NSABP-B31 and NCCTG N9831), employed anthracycline-containing regimens with sequential paclitaxel, with or without trastuzumab. The third study, HERA trial, randomized patients after adjuvant chemotherapy into an observational arm, one or two years of trastuzumab. Results of these studies, after a median follow up of 2-3 years confirm a DFS and OS benefit for the experimental arms. The worst rate of cardiotoxicity, in terms of incidence of CHF, with the use of trastuzumab and anthracycline based regimens was 4.1% in the trastuzumab arm of the NSABP-B31 trial. Among the fi ve trastuzumab trials, two, BCIRG 006 and FinHer, employed docetaxel-based regimens. The innovative BCIRG 006 trial compared ACdocetaxel (T) with two trastuzumab-containing regimens, ACTH, and a non-anthracycline-containing regimens, TCH, with a clear advantage in DFS for both trastuzumab arms. Data from the second interim analysis indicate that, in the subgroup of patients without co-amplification of topoisomerase 2 (TOPO-2), the arm without trastuzumab (ACT) showed a DFS significantly poorer that in the other arms; moreover, if we consider the lower toxicity of TCH regimen in comparison with anthracycline-containing arms, the innovative statements offered by BCIRG 006 trial appear evident, and these findings opened an important question about the consolidated employment of anthracyclines in adjuvant setting.The FinHer trial was a small trial testing a short course of trastuzumab (9 weeks) concomitantly with a chemotherapy including docetaxel, and there was a significant advantage in DFS for the trastuzumab based arms, without relevant toxicity and without any cardiotoxicity. Although data from all trastuzumab adjuvant trials, and without particulary from BCIRG-006 and FinHer trials, appear very intriguing, further follow-up is required.

Optimal sequence of anthracyclines and taxanes as adjuvant breast cancer treatment.

Results from randomized trials evaluating taxane versus non-taxane containing regimens in adjuvant breast cancer treatment indicate an advantage in DFS and OS for the taxane-arms, but the best schedule of administration, in combination with anthracyclines or in sequence, is still a debated issue, even if the sequential strategy appears to be less toxic. Up to now, the majority of clinical trials employed the "standard" sequence, with anthracycline-based combinations fi rst, followed by taxanes. Few small phase II trials evaluated the reverse sequence, with taxanes administered fi rst, most of them in metastatic or neoadjuvant setting, suggesting efficacy and lower toxicity. An important issue to be considered is the hypothesized differences in the ability of the drugs to induce cross-resistance to each other, as suggested by data of a preclinical study, and from clinical study with a cross-over design; results of these trials suggest that the best strategy would be to administer a taxane prior to an anthracycline, also according to the Norton and Simon hypothesis. Moreover, trials evaluating the best sequence of anthracyclines and taxanes in adjuvant breast cancer setting are of small sample size, and an adequately powered randomized phase III trial is needed before definitive conclusions are reached.

[Optimal role of docetaxel in adjuvant chemotherapy for early stage HER2-negative breast cancer]. / Uso ottimale del docetaxel nella chemioterapia adiuvante delle pazienti con carcinoma mammario HER2-negativo.

The fundamental imperative of adjuvant treatment of early breast cancer is to improve long-term survival and minimize toxicity. The inclusion of docetaxel in adjuvant chemotherapy regimens has improved patient survival in comparison to anthracycline-containing regimens, even if the incidence of acute side effects has increased in some studies. However, late or persistent toxic effects are becoming more important due to an increasing proportion of patients remaining disease free after treatment for early breast cancer. Several studies have recently reported that docetaxel-containing regimens without anthracyclines are equally active, and have no apparent cardiotoxicity. At present, docetaxel-based combinations represent an appropriate choice in the adjuvant treatment of HER2-negative breast cancer, and several studies are ongoing aiming at a better evaluation of the efficacy of this agent in order to optimize its role.

[High-dose CEF (cyclophosphamide, epirubicin, fluorouracil) as primary chemotherapy in locally advanced breast cancer: long-term results]. / CEF (ciclofosfamide, epirubicina, fluorouracile) ad alte dosi come chemioterapia primaria nel trattamento del carcinoma mammario localmente avanzato: risultati a lungo termine.

PURPOSE: 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). MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Irinotecan, docetaxel and oxaliplatin combination in metastatic gastric or gastroesophageal junction adenocarcinoma.

This phase II study was designed to evaluate the activity and safety of a combination of irinotecan, docetaxel and oxaliplatin in metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. Forty patients with measurable distant metastasis received irinotecan 150 mg m(-2) and docetaxel 60 mg m(-2) on day 1, and oxaliplatin 85 mg m(-2) on day 2. Cycles were repeated every 3 weeks. The primary end point was to demonstrate a 50% improvement in time-to-progression (TTP) over historical controls. All patients were evaluable. Median TTP was 6.5 months (95% confidence interval (CI) 5.6-7.4), the overall response rate was 50% (95% CI 35-65%) and the median overall survival was 11.5 months (95% CI 8.7-14.3). Grade 3/4 neutropaenia occurred in 47.5% of patients. There were four episodes of febrile neutropaenia in three patients. Other non-haematological grade 3 toxicities included diarrhoea in four patients (10%), vomiting in three patients (7.5%) and mucositis in two patients (5%). The irinotecan, docetaxel and oxaliplatin combination chemotherapy is an active and well-tolerated novel regimen for treating metastatic gastric or GEJ adenocarcinoma and deserves further evaluation in randomised trials and in combination with molecular targeting agents.

Epirubicin, cisplatin and docetaxel combination therapy for metastatic gastric cancer.

BACKGROUND: Docetaxel is a new agent with activity in metastatic gastric cancer. This phase II study was designed to evaluate the activity and safety of an epirubicin, cisplatin and docetaxel combination in patients with this disease. PATIENTS AND METHODS: Forty-six patients with gastric adenocarcinoma with measurable distant metastasis were eligible for the study. Patients received epirubicin 50 mg/m(2) and docetaxel 60 mg/m(2), on day 1, and cisplatin 60 mg/m(2) on day 2. Granulocyte colony-stimulating factor 300 mug/day subcutaneously was given on days 5 and 6. Cycles were repeated every 3 weeks for a maximum of eight courses. RESULTS: All patients were evaluable for response and toxicity. Two complete and 21 partial responses were observed, with an overall response rate of 50% [95% confidence interval (CI) 36% to 64%]. Stable disease was observed in 13 patients (28%) and progressive disease in 10 patients (22%). The median time to progression was 6 months (95% CI 5-7) and the median overall survival was 11.2 months (95% CI 8.5-13.9). Grade 3/4 neutropenia, thrombocytopenia and anemia occurred in 46%, 7% and 13% of patients, respectively. There were five episodes of febrile neutropenia in four patients. Other grade 3 toxicities included mucositis in three patients (6.5%), vomiting in four patients (8.7%) and diarrhea in one patient (2%). There were no cardiac toxicity, severe neurotoxicity or treatment-related deaths. CONCLUSIONS: The epirubicin, cisplatin and docetaxel combination is an active and well tolerated novel chemotherapy regimen for treating metastatic gastric cancer and deserves further evaluation in randomized studies.

[The treatment of osteodystrophy in dialyzed uremic patients: results of the first Sardinian audit]. / Il trattamento dell'osteodistrofia nei pazienti uremici in dialisi: risultati del primo Audit sardo.

BACKGROUND: Hyperphosphatemia in the uremic patient undergoing dialysis causes and makes the secondary hyperpharatyroidism progress. Nowadays it has a very important role in predicting mortality. The aim of the study was to assess by "Audit" to analyse adequacy of the Sardinian dialytic patients with reference to the optimal objective of the national and international guidelines. PATIENTS AND METHODS: The questionnaire of the audit was composed of 11 questions about the percentage distribution of: calcium in the dialysate, values of phosphoremia), Ca x P product, patients treated with vitamin D taking one or more phosphate binders, average dose, spKt/V > or = 1.2, serum aluminium, parathiroidectomy. RESULTS: We examined 1274 dialysis patients (93% on hemodialysis and 7% in CAPD) in 26 dialytic centers in our region (age 63.8 anni +/- 32.4; dialytic age 5.15 +/- 5.06. Phosphorus ranges (mg/dL) P < 5.5: 61.3 +/- 23%; between 5.5 e 6.5: 28.2 +/- 17.7%; and P > 6.5: 10.4 +/- 7.7%; Ca x P (<60): 77.8% +/- 16.6%; between 60-70: 16.8 +/- 13.4%; > 70: 4.99 +/- 4.7%. The more prescribed dialysate calcium was 1.5 mmol/L in HD (58.8%) HF (60.6%), HDF (51.6%) and CAPD (5.6%). PTH levels were: 31.1% (<120); 29.5% (120-250); 21.1% (250-450); 8% (450-600); 10.3% (>600). Patients on vitamin D: os daily 23.04 +/- 28%; post-dialysis boluses: os 32.6 +/- 28, i.v. 10.6 +/- 9%; no therapy 32.7 +/- 22.7%. The percentage use of phosphorus binders: 48.5% calcium carbonate (2.9 g/d); 7.12% calcium acetate (1.34 g/d); 13.5% sevelamer (2.79 g/d); 10% total aluminium based (0.62 g/d). The aluminium is dosed in 11/26 dialysis units (32.3% of the population); 2.3% +/- 0.9% of patients having Aluminium > 30 mcg/L. The dialytic patients have a Kt/V > or = 1.2: 80.1 +/- 19%. Parathyroidectomy incidences 1.8%. CONCLUSIONS: The data show good control of the average phosporous, there is a worrying percentage of patients with PTH values compatible with hypodynamic bone condition, lower and therefore safer calcium levels in the dialysate, poor aluminium control and low incidence of parathyroidectomy. In our experience the audit is a good way to verify and to correct the therapeutic choice in uremic osteodistrophy.

Docetaxel in patients with anthracycline-resistant advanced breast cancer.

OBJECTIVE: To better determine docetaxel activity in patients with well-defined anthracycline-resistant breast cancer. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

First-line chemotherapy with vinorelbine and paclitaxel as simultaneous infusion in advanced breast cancer.

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.