... non-Hodgkin's lymphoma. Acknowledgements. The authors would like to thank Dr.Marco P... more ... non-Hodgkin's lymphoma. Acknowledgements. The authors would like to thank Dr.Marco Paulli (Pathology Unit, IRCCSS S. Matteo, University of Pavia, Italy) for histologic review of the immunocytomas. References. 1 MS De ...
The aim of this study was to evaluate the effectiveness and the safety of percutaneous radiofrequ... more The aim of this study was to evaluate the effectiveness and the safety of percutaneous radiofrequency (RF) thermal ablation of hepatocellular carcinoma (HCC) in 88 patients with a long follow-up, and to compare conventional electrodes and expandable electrodes. Eighty-eight patients with 101 hepatocellular carcinoma nodules (≤ 3.5 cm in diameter) underwent RF thermal ablation by means of either conventional electrodes or an expandable electrode. Therapeutic efficacy was evaluated with dynamic contrast CT, serum α-feto protein level, US examination at the end of the treatment, and during follow-up. Complete necrosis was obtained in all tumor nodules in a mean number of 3.3 sessions (tumor treated by conventional electrodes) or 1.5 sessions (tumor treated by expandable electrode). The mean follow-up was 34 months; overall survival rate was 33 % at 5 years. Disease-free survival at 5 years was 3 %; local recurrence rate was 29 % in patients treated with conventional electrodes; 14 % in patients treated with the expandable electrode. Two major complications and 14 minor complications were observed. Radiofrequency thermal ablation in small HCC is very effective with a low percentage of major complications. The use of an expandable electrode substantially reduced the number of treatment sessions but did not modify the overall survival rate and the disease-free survival rate.
The incidence of melanoma has increased continuously during the last decade. Surgery is the mains... more The incidence of melanoma has increased continuously during the last decade. Surgery is the mainstay of therapy but, for patients with thick lesions or regional metastatic lymph nodes, there is a high risk of relapse. For this group of patients, there is no standard therapy or general agreement amongst oncologists. In this article, we review the current management of melanoma with regard to past completed adjuvant trials and open trials. Moreover, we discuss the role of chemotherapy in metastatic melanoma, in particular with attention to the use of fotemustine.
Background: Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on... more Background: Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on tumor cells. Alternative mechanisms of efficacy have been ascribed to several common anticancer agents, including cyclophosphamide (CTX), methotrexate (MTX), anthracyclines and taxanes, postulating an antiangiogenic activity.
Background: HER2/neu overexpression is linked to promotion of angiogenesis in breast cancer. We t... more Background: HER2/neu overexpression is linked to promotion of angiogenesis in breast cancer. We therefore tested the activity of the combination of Trastuzumab with metronomic, low dose chemotherapy with cyclophosphamide (CTX) and methotrexate (MTX) in metastatic breast cancer (MBC).
Background No specific treatment guidelines are available for triple-negative breast cancers, def... more Background No specific treatment guidelines are available for triple-negative breast cancers, defined by a lack of expression of estrogen (ER), progesterone (PgR), and HER2 receptors. Patients and methods We investigated in patients with T2–T3 N0-3 ER, PgR <10% and HER2 negative breast cancers the activity both in terms of pathological (pCR) and objective responses of four courses of cisplatin containing chemotherapy (ECF, epirubicin, cisplatin, and fluorouracil as continuous infusion) followed by three courses of weekly paclitaxel. Adjuvant metronomic chemotherapy including cyclophosphamide and methotrexate for 4–6 months was administered. Results Thirty patients are evaluable. Median age was 41 years (28–64 years). Twenty-three of 25 evaluable tumors stained positively for epidermal growth factor receptor. An objective response, either complete and partial, was observed in 26 patients (86, 95% CI 69.3–96.2%). and a pCR was obtained in 12 patients (40, 95% CI 22.7–59.4%). Two patients progressed during paclitaxel. Negative axillary nodes were found in 80% (95% CI 61.4–92.3%) of patients at surgery. Twenty-six patients (86, 95% CI 61.4–92.3%) underwent breast conserving surgery. Grade >2 non-hematological toxicity was observed in three and two patients during ECF and paclitaxel, respectively. The 2-year disease free survival (DFS) was 87.5% (95% CI 74.7–100%). No significant correlation was observed between EGFR staining and either pCR or DFS. Conclusions Preoperative cisplatin containing chemotherapy followed by paclitaxel induced an high pCR rate in a population of triple-negative breast cancer. The impact of this schedule on long-term outcome should be investigated in larger series.
The aim of this study was to investigate in a randomized trial the activity of perioperative chem... more The aim of this study was to investigate in a randomized trial the activity of perioperative chemotherapy in patients treated with preoperative chemotherapy for locally advanced breast cancer and to compare it with the preoperative chemotherapy alone. Patients with cT2-3 N0-2 M0 histologically proven breast cancer, with estrogen receptors and progesterone receptors in less than 20% of cells, or with absence of progesterone receptors, received epirubicin 25 mg/m days 1 and 2, cisplatin 60 mg/m day 1, and fluorouracil 200 mg/m daily as continuous infusion. Responding patients were randomized to continue fluorouracil until 2 weeks after surgery (perioperative chemotherapy) or to stop fluorouracil 1 week before surgery. Fifty-eight patients completed six courses of epirubicin, cisplatin and fluorouracil, and were randomized to perioperative chemotherapy (29 patients) or to control (29 patients). The median Ki-67 index remained stable (32-27.5%) in the perioperative chemotherapy arm (P=0.3) and decreased from 55 to 22.5% in the control arm (P=0.01). The rate of pathological complete remission was 41% in both arms (P=1.0). No significant difference in terms of disease-free survival and overall survival was observed between the two arms. Perioperative chemotherapy failed to show an increase in the pathological complete remission rate. A biological effect on Ki-67 expression was demonstrated.
Purpose Second-line chemotherapy in patients with metastatic gastric cancer (MGC) pre-treated wit... more Purpose Second-line chemotherapy in patients with metastatic gastric cancer (MGC) pre-treated with cisplatin is not a standard option. We studied a combination of irinotecan, fluorouracil and folates. Methods Patients progressive to cisplatin-based chemotherapy were enrolled. Irinotecan 180 mg/m2, folinic acid 200 mg/m2, and fluorouracil 400 mg/m2 were given on day 1, immediately followed by fluorouracil 2,400 mg/m2 46 h continuous infusion (simplified FOLFIRI), every 2 weeks. Results Between June 2002 and May 2003, 28 patients were treated. Median age was 57 years (range 38–68). Most patients had a distal primary (90%), and metastatic disease (71%). Partial response was obtained in six patients (21%, 95% CI 8–41) and stable disease in eight (21%, 95% CI 13–41). Among the six responsive patients three were refractory to docetaxel. At a median follow-up of 2.9 years median time to progression was 4 months (95% CI: 2–5), and median overall survival was 5 months (95% CI 4–9). Toxicity was mild, without treatment-related deaths or life-treating adverse events. Conclusions Simplified FOLFIRI was moderately active and well tolerated in unselected patients with MGC pre-treated with cisplatin-based chemotherapy. Its role in patients refractory to taxanes is promising and warrants further investigation.
Dear Editor,We would comment the unpredictable results of the recent article by Hiromichi Ishiyam... more Dear Editor,We would comment the unpredictable results of the recent article by Hiromichi Ishiyama et al. [1]. If it could be acceptable that external radiotherapy scarcely affects morphine doses, this paper deserves some methodological observations.First, the authors do not report any data about the intensity of pain before and after the radiotherapy treatment. It is a common fact that some cancer therapies (e.g., radiotherapy) may not reduce analgesic drugs consumption but may reduce pain intensity, indeed, allowing a better symptomatic control by the same, previously ineffective analgesic treatment. For this reason, the authors’ statement that “An increase in morphine dose thus means that the patient has pain, while a decrease means that the patient has little pain” seems difficult to be justified according to the paper context.Second, we do not know the qualities of the pains treated. Were patients affected by incident pain episodes, or was a neuropathic pain present? We know how o
Breast manipulation determines a physiological increase in prolactin (PRL) blood levels, but the ... more Breast manipulation determines a physiological increase in prolactin (PRL) blood levels, but the clinical and biological impact of surgery-induced changes in PRL secretion still has to be clarified. The postoperative hyperprolactinemia has been related to aggressiveness of the tumor, early disease relapse or metastases, and poor overall survival in node-negative breast cancer patients. Surgery-induced hyperprolactinemia may be associated with a longer disease-free survival in both patients with or without node involvement. One hundred twenty-seven consecutive node-negative breast cancer patients, who were hospitalized from June 1985 to September 1990, were included in this study. The median follow-up was 12 years. To evaluate PRL secretion, venous blood samples were obtained at day 7th after surgery. In order to exclude the influence of stress and gonadal status, GH and estradiol serum levels were measured in the same blood samples. All endocrine examination were made during the morning, starting at 8.00 a.m. after overnight fasting. Hormonal serum levels were determined by the double antibody radioimmunoassay method. Hyperprolactinemia was significantly more frequent in women younger than 50 years compared with the older ones, while the premenopausal status and T1 stage showed only a borderline significant association with hyperprolactinemia. Patients with normal postsurgical prolactinemia had 5- and 10-year disease-free survival rates of 64 and 56%, respectively, and 5- and 10-year overall survival rates of 84 and 70%, respectively. Patients with postsurgical hyperprolactinemia had 5- and 10-year disease-free survival rates of 89 and 81%, respectively, and 5- and 10-year overall survival rates of 94 and 81%, respectively. The difference in overall survival between the hyperprolactinemic and the normoprolactinemic groups, assessed by the log-rank test, was statistically significant (p = 0.02), and the difference in disease-free survival was highly significant (p = 0.0008). Our study shows that postsurgical hyperprolactinemia is associated with a significantly lower recurrence rate and longer disease-free and overall survival in operable node-negative breast cancer patients. Our data suggest that postoperative hyperprolactinemia could be crucial in the development of recurrence in operable breast cancer. Looking at results, the recurrence rate of node-negative patients who did not show postoperative hyperprolactinemia would be, in theory, similar to that of patients with node-positive disease, suggesting that normal postoperative PRL levels could identify a group of node-negative patients at high risk for recurrence.
Background: Despite numerous randomized trials suggesting a benefit of unconventional fractionati... more Background: Despite numerous randomized trials suggesting a benefit of unconventional fractionation in locally advanced head and neck cancer, the role of this approach in nasopharyngeal carcinoma is debatable. Based on the current clinical experience, the authors introduced hyperfractionated irradiation in the treatment of locally advanced head and neck cancer, including nasopharyngeal tumors. The preliminary results of this treatment approach in nasopharyngeal cancer patients are presented, with special focus on the pattern of failure and toxicity. Patients and Methods: 43 patients with nasopharyngeal cancer (stage II–IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy was preceded by a median of three cycles of cisplatin-based induction chemotherapy. Irradiation was delivered using a shrinking-field technique up to a total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h interval)/5 days/week. Results: Acute toxicity of hyperfractionated radiotherapy was significant but tolerable. Mucositis proved the most common side effect (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks after completion of radiotherapy, complete response was seen in 35 patients (81%), partial response in five (12%), stable disease in one, and progressive disease in two. After a median follow-up of 32 months, 18 patients (41%) developed progressive disease. Primary tumor progression was observed in three patients, and seven patients each showed regional lymph node progression and distant metastases. In one case both regional lymph node progression and distant metastases were diagnosed. The 2-year progression-free survival and overall survival rates were 58% and 84%, respectively. Conclusion: Hyperfractionated radiotherapy seems a feasible and active regimen in locally advanced nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and does not compromise delivery of the planned irradiation dose. This regimen is associated with a high local control rate; relatively high nodal and distant failure, however, call for further treatment modifications, e. g., optimization of irradiation technique and/or dose escalation as well as improved systemic therapies. Hintergrund: Obwohl zahlreiche randomisierte Studien zugunsten unkonventioneller Fraktionierungsschemata bei lokal fortgeschrittenenen Kopf-Hals-Tumoren sprechen, ist der Stellenwert dieses Vorgehens beim Nasopharynxkarzinom umstritten. Auf der Basis gängiger klinischer Erfahrung führten die Autoren die hyperfraktionierte Bestrahlung in die Therapie lokal fortgeschrittener Kopf-Hals-Tumoren, einschließlich Nasopharynxkarzinome, ein. Erste Ergebnisse dieses Therapieansatzes bei Patienten mit Nasopharynxkarzinom werden vorgestellt und insbesondere Grenzen des Verfahrens und seine Toxizität diskutiert. Patienten und Methodik: 43 Patienten mit Nasopharynxkarzinom (Stadium II–IV, TNM 1997) erhielten eine hyperfraktionierte Strahlentherapie. In 34 Fällen gingen der Bestrahlung im Mittel drei Zyklen einer Cisplatin-basierten Induktionschemotherapie voraus. Die Strahlentherapie wurde im Rahmen einer „Shrinking-Field-Technik“ bis zu einer Gesamtdosis von 74,4 Gy in 62 Fraktionen mit 2× täglich 1,2 Gy (Minimum 6-h-Interval) an 5 Tagen pro Woche durchgeführt. Ergebnisse: Die Akuttoxizität der hyperfraktionierten Strahlentherapie war bedeutend, aber tolerabel. Häufigste Nebenwirkung war die Mukositis (Grad 3: 24 Patienten, Grad 4: drei Patienten). Schwerwiegende Spättoxizitäten wurden nicht festgestellt. 30 von 34 Patienten (88%) sprachen auf die Induktionschemotherapie an. 6 Wochen nach Abschluss der Strahlentherapie, wurde eine komplette Remission bei 35 Patienten (81%) beobachtet, partielles Ansprechen bei fünf (12%), Krankheitsstillstand bei einem und Fortschreiten der Erkrankung bei zwei Patienten. Nach im Median 32 Monaten Follow-up zeigte sich bei 18 Patienten (41%) eine Progression der Erkrankung. Fortschreiten des Primärtumors wurde bei drei Patienten beobachtet, und sieben Patienten wiesen entweder Befall der regionalen Lymphknoten oder Fernmetastasen auf. In einem Fall wurden sowohl Befall der regionalen Lymphknoten als auch Fernmetastasen diagnostiziert. Das progressionsfreie Überleben und Gesamtüberleben nach 2 Jahren waren 58% bzw. 84%. Schlussfolgerung: Die hyperfraktionierte Strahlentherapie scheint bei lokal fortgeschrittenem Nasopharynxarzinom praktikabel und wirksam zu sein. Die auftretende Akut- und Spättoxizität ist akzeptabel und gefährdet die Verabreichung der geplanten Strahlungsdosis nicht. Dieses Vorgehen führt zu einer hohen lokalen Kontrolle; allerdings verlangt das relativ hohe regionale und systemische Therapieversagen weitere Modifikationen, z. B. die Optimierung der Bestrahlungstechnik und/oder Dosisekalation sowie verbesserte systemische Therapien.
The aim of this study was to assess the potential of perfusion computed tomography (CTp) for moni... more The aim of this study was to assess the potential of perfusion computed tomography (CTp) for monitoring induction chemotherapy in patients with squamous cell carcinoma (SCCA) of the upper aerodigestive tract. Twenty-five patients with advanced SCCA underwent CTp and volumetric CT before and after induction chemotherapy. Perfusion CT parameters were calculated in the tumor, normal tissue, and muscles and correlated with tumor volume. The blood flow (BF), blood volume (BV), and permeability surface were significantly higher, and the mean transit time was significantly lower in the tumor than in the normal tissue. The tumor BF and BV significantly decreased, and the mean transit time significantly increased after the therapy; decrease in BF and BV correlated with tumor volume reduction after chemotherapy. The baseline tumor BV was significantly lower in nonresponders compared with that in responders. In patients with SCCA, CTp showed potential for monitoring induction chemotherapy, reduction in tumor BF and BV correlated with reduction of tumor volume after chemotherapy, and baseline tumor BV may predict response to chemotherapy.
The clinical efficacy and antiangiogenic effect of low-dose, metronomic administration of cycloph... more The clinical efficacy and antiangiogenic effect of low-dose, metronomic administration of cyclophosphamide (CTX) and methotrexate (MTX) (CM) have been demonstrated. The authors report results and long-term follow-up for patients with metastatic breast carcinoma who obtained prolonged clinical benefit with CM. Prospectively collected data from two successive clinical trials were evaluated. From July 1997 to October 2003, patients with metastatic breast carcinoma were treated with low-dose oral chemotherapy (MTX 2.5 mg, twice daily on day 1 and day 2 or 4, and CTX 50 mg daily). Patients who achieved prolonged clinical benefit for a duration of 12 months or more (complete remission, partial remission or stabilization of disease) were considered for the analysis. Median follow-up was 23 months. A total of 153 patients were enrolled and are evaluable: Eastern Cooperative Oncology Group performance status 0-1 in 90 patients, two or more sites of metastatic disease in 97 patients, zero regimen for metastatic breast carcinoma in 48 patients. Among 153 patients, five demonstrated complete remission and 25 partial remission. The proportion of patients who achieved prolonged clinical benefit was 15.7% (95% confidence interval 9.9-21.4%). Median time to progression for patients with prolonged clinical benefit was 21 months (range 12-37+ months). One patient maintained complete remission 42 months after therapy discontinuation. At the multivariate analysis endocrine responsiveness and the achievement of an objective response significantly correlated with the achievement of prolonged clinical benefit. Metronomic chemotherapy can induce prolonged clinical benefit in metastatic breast cancer, supporting its role as an additional therapeutic tool in the treatment of patients with metastatic breast carcinoma.
alpha-Interferon, thalidomide and celecoxib inhibit tumour angiogenesis by differing mechanisms. ... more alpha-Interferon, thalidomide and celecoxib inhibit tumour angiogenesis by differing mechanisms. In a randomized phase II trial to assess tolerability and safety, we assigned patients with advanced slow-growing solid tumours to 1 of 6 two- or three-drug combinations: alpha-interferon 0.5 million IU b.i.d., thalidomide (100 mg b.i.d. reduced to 100 mg daily), or celecoxib (400 mg daily reduced to 200 mg). Circulating endothelial cells and progenitors (CECs, CEPs) and vascular endothelial growth factor were also studied. From January 2002 to September 2005, 62 patients were enrolled. Four months after initiating treatment, 3 (4%) had partial response, 40 (64%) had stable disease and 19 (30%) had disease progression. Median duration of clinical benefit (partial response/stable disease) was 11.3 months. Patients receiving a third drug had significantly less stable disease plus partial response (chi(2) test, p = 0.002) than those receiving two drugs. The treatments were generally well tolerated, but neurotoxicity (G3 lethargy) occurred in 6 patients. Baseline CEPs were lower (p = 0.004) in patients with clinical benefit at 6 months than those without benefit. After 2 months of treatment CECs were lower than at baseline (p = 0.018) in patients without clinical benefit, and CEPs were higher than at baseline (p = 0.003) in patients with benefit. In pretreated patients with advanced slow-growing solid tumours, long-term metronomic administration of two-drug combinations of alpha-interferon, thalidomide or celecoxib was well tolerated and had antitumour activity. Low baseline CEPs in patients with subsequent clinical benefit suggest that CEC count may identify patients likely to benefit from long-term metronomic anti-angiogenic treatment.
Endothelium-journal of Endothelial Cell Research, 2008
High altitude and hypoxia are known to induce polycythemia, pulmonary hypertension, and vascular ... more High altitude and hypoxia are known to induce polycythemia, pulmonary hypertension, and vascular remodeling. The authors investigated a number of blood cell populations in 15 mountain trekkers before and after 12 days spent at &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;3000 m. Red blood cell and platelet count increased, whereas circulating hematopoietic stem cell (enumerated as CD34bright cells), circulating endothelial cell (CEC) and circulating endothelial progenitor (CEP) count significantly decreased. In particular, the authors observed a decrease in the count of viable CECs, and a decrease in the circulating levels of RNA of the endothelial-specific gene VE-cadherin, whereas the fraction of apoptotic/necrotic CECs was stable. These data suggest a unique pattern of modulation of surrogate markers of vascular remodeling induced by exposure to hypobaric hypoxia.
Es una respuesta biológica producida por el organismo como respuesta a determinados estímulos, fu... more Es una respuesta biológica producida por el organismo como respuesta a determinados estímulos, fundamentalmente al estrés. La sonrisa se considera una forma suave y silenciosa de risa.
... non-Hodgkin&#x27;s lymphoma. Acknowledgements. The authors would like to thank Dr.Marco P... more ... non-Hodgkin&#x27;s lymphoma. Acknowledgements. The authors would like to thank Dr.Marco Paulli (Pathology Unit, IRCCSS S. Matteo, University of Pavia, Italy) for histologic review of the immunocytomas. References. 1 MS De ...
The aim of this study was to evaluate the effectiveness and the safety of percutaneous radiofrequ... more The aim of this study was to evaluate the effectiveness and the safety of percutaneous radiofrequency (RF) thermal ablation of hepatocellular carcinoma (HCC) in 88 patients with a long follow-up, and to compare conventional electrodes and expandable electrodes. Eighty-eight patients with 101 hepatocellular carcinoma nodules (≤ 3.5 cm in diameter) underwent RF thermal ablation by means of either conventional electrodes or an expandable electrode. Therapeutic efficacy was evaluated with dynamic contrast CT, serum α-feto protein level, US examination at the end of the treatment, and during follow-up. Complete necrosis was obtained in all tumor nodules in a mean number of 3.3 sessions (tumor treated by conventional electrodes) or 1.5 sessions (tumor treated by expandable electrode). The mean follow-up was 34 months; overall survival rate was 33 % at 5 years. Disease-free survival at 5 years was 3 %; local recurrence rate was 29 % in patients treated with conventional electrodes; 14 % in patients treated with the expandable electrode. Two major complications and 14 minor complications were observed. Radiofrequency thermal ablation in small HCC is very effective with a low percentage of major complications. The use of an expandable electrode substantially reduced the number of treatment sessions but did not modify the overall survival rate and the disease-free survival rate.
The incidence of melanoma has increased continuously during the last decade. Surgery is the mains... more The incidence of melanoma has increased continuously during the last decade. Surgery is the mainstay of therapy but, for patients with thick lesions or regional metastatic lymph nodes, there is a high risk of relapse. For this group of patients, there is no standard therapy or general agreement amongst oncologists. In this article, we review the current management of melanoma with regard to past completed adjuvant trials and open trials. Moreover, we discuss the role of chemotherapy in metastatic melanoma, in particular with attention to the use of fotemustine.
Background: Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on... more Background: Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on tumor cells. Alternative mechanisms of efficacy have been ascribed to several common anticancer agents, including cyclophosphamide (CTX), methotrexate (MTX), anthracyclines and taxanes, postulating an antiangiogenic activity.
Background: HER2/neu overexpression is linked to promotion of angiogenesis in breast cancer. We t... more Background: HER2/neu overexpression is linked to promotion of angiogenesis in breast cancer. We therefore tested the activity of the combination of Trastuzumab with metronomic, low dose chemotherapy with cyclophosphamide (CTX) and methotrexate (MTX) in metastatic breast cancer (MBC).
Background No specific treatment guidelines are available for triple-negative breast cancers, def... more Background No specific treatment guidelines are available for triple-negative breast cancers, defined by a lack of expression of estrogen (ER), progesterone (PgR), and HER2 receptors. Patients and methods We investigated in patients with T2–T3 N0-3 ER, PgR <10% and HER2 negative breast cancers the activity both in terms of pathological (pCR) and objective responses of four courses of cisplatin containing chemotherapy (ECF, epirubicin, cisplatin, and fluorouracil as continuous infusion) followed by three courses of weekly paclitaxel. Adjuvant metronomic chemotherapy including cyclophosphamide and methotrexate for 4–6 months was administered. Results Thirty patients are evaluable. Median age was 41 years (28–64 years). Twenty-three of 25 evaluable tumors stained positively for epidermal growth factor receptor. An objective response, either complete and partial, was observed in 26 patients (86, 95% CI 69.3–96.2%). and a pCR was obtained in 12 patients (40, 95% CI 22.7–59.4%). Two patients progressed during paclitaxel. Negative axillary nodes were found in 80% (95% CI 61.4–92.3%) of patients at surgery. Twenty-six patients (86, 95% CI 61.4–92.3%) underwent breast conserving surgery. Grade >2 non-hematological toxicity was observed in three and two patients during ECF and paclitaxel, respectively. The 2-year disease free survival (DFS) was 87.5% (95% CI 74.7–100%). No significant correlation was observed between EGFR staining and either pCR or DFS. Conclusions Preoperative cisplatin containing chemotherapy followed by paclitaxel induced an high pCR rate in a population of triple-negative breast cancer. The impact of this schedule on long-term outcome should be investigated in larger series.
The aim of this study was to investigate in a randomized trial the activity of perioperative chem... more The aim of this study was to investigate in a randomized trial the activity of perioperative chemotherapy in patients treated with preoperative chemotherapy for locally advanced breast cancer and to compare it with the preoperative chemotherapy alone. Patients with cT2-3 N0-2 M0 histologically proven breast cancer, with estrogen receptors and progesterone receptors in less than 20% of cells, or with absence of progesterone receptors, received epirubicin 25 mg/m days 1 and 2, cisplatin 60 mg/m day 1, and fluorouracil 200 mg/m daily as continuous infusion. Responding patients were randomized to continue fluorouracil until 2 weeks after surgery (perioperative chemotherapy) or to stop fluorouracil 1 week before surgery. Fifty-eight patients completed six courses of epirubicin, cisplatin and fluorouracil, and were randomized to perioperative chemotherapy (29 patients) or to control (29 patients). The median Ki-67 index remained stable (32-27.5%) in the perioperative chemotherapy arm (P=0.3) and decreased from 55 to 22.5% in the control arm (P=0.01). The rate of pathological complete remission was 41% in both arms (P=1.0). No significant difference in terms of disease-free survival and overall survival was observed between the two arms. Perioperative chemotherapy failed to show an increase in the pathological complete remission rate. A biological effect on Ki-67 expression was demonstrated.
Purpose Second-line chemotherapy in patients with metastatic gastric cancer (MGC) pre-treated wit... more Purpose Second-line chemotherapy in patients with metastatic gastric cancer (MGC) pre-treated with cisplatin is not a standard option. We studied a combination of irinotecan, fluorouracil and folates. Methods Patients progressive to cisplatin-based chemotherapy were enrolled. Irinotecan 180 mg/m2, folinic acid 200 mg/m2, and fluorouracil 400 mg/m2 were given on day 1, immediately followed by fluorouracil 2,400 mg/m2 46 h continuous infusion (simplified FOLFIRI), every 2 weeks. Results Between June 2002 and May 2003, 28 patients were treated. Median age was 57 years (range 38–68). Most patients had a distal primary (90%), and metastatic disease (71%). Partial response was obtained in six patients (21%, 95% CI 8–41) and stable disease in eight (21%, 95% CI 13–41). Among the six responsive patients three were refractory to docetaxel. At a median follow-up of 2.9 years median time to progression was 4 months (95% CI: 2–5), and median overall survival was 5 months (95% CI 4–9). Toxicity was mild, without treatment-related deaths or life-treating adverse events. Conclusions Simplified FOLFIRI was moderately active and well tolerated in unselected patients with MGC pre-treated with cisplatin-based chemotherapy. Its role in patients refractory to taxanes is promising and warrants further investigation.
Dear Editor,We would comment the unpredictable results of the recent article by Hiromichi Ishiyam... more Dear Editor,We would comment the unpredictable results of the recent article by Hiromichi Ishiyama et al. [1]. If it could be acceptable that external radiotherapy scarcely affects morphine doses, this paper deserves some methodological observations.First, the authors do not report any data about the intensity of pain before and after the radiotherapy treatment. It is a common fact that some cancer therapies (e.g., radiotherapy) may not reduce analgesic drugs consumption but may reduce pain intensity, indeed, allowing a better symptomatic control by the same, previously ineffective analgesic treatment. For this reason, the authors’ statement that “An increase in morphine dose thus means that the patient has pain, while a decrease means that the patient has little pain” seems difficult to be justified according to the paper context.Second, we do not know the qualities of the pains treated. Were patients affected by incident pain episodes, or was a neuropathic pain present? We know how o
Breast manipulation determines a physiological increase in prolactin (PRL) blood levels, but the ... more Breast manipulation determines a physiological increase in prolactin (PRL) blood levels, but the clinical and biological impact of surgery-induced changes in PRL secretion still has to be clarified. The postoperative hyperprolactinemia has been related to aggressiveness of the tumor, early disease relapse or metastases, and poor overall survival in node-negative breast cancer patients. Surgery-induced hyperprolactinemia may be associated with a longer disease-free survival in both patients with or without node involvement. One hundred twenty-seven consecutive node-negative breast cancer patients, who were hospitalized from June 1985 to September 1990, were included in this study. The median follow-up was 12 years. To evaluate PRL secretion, venous blood samples were obtained at day 7th after surgery. In order to exclude the influence of stress and gonadal status, GH and estradiol serum levels were measured in the same blood samples. All endocrine examination were made during the morning, starting at 8.00 a.m. after overnight fasting. Hormonal serum levels were determined by the double antibody radioimmunoassay method. Hyperprolactinemia was significantly more frequent in women younger than 50 years compared with the older ones, while the premenopausal status and T1 stage showed only a borderline significant association with hyperprolactinemia. Patients with normal postsurgical prolactinemia had 5- and 10-year disease-free survival rates of 64 and 56%, respectively, and 5- and 10-year overall survival rates of 84 and 70%, respectively. Patients with postsurgical hyperprolactinemia had 5- and 10-year disease-free survival rates of 89 and 81%, respectively, and 5- and 10-year overall survival rates of 94 and 81%, respectively. The difference in overall survival between the hyperprolactinemic and the normoprolactinemic groups, assessed by the log-rank test, was statistically significant (p = 0.02), and the difference in disease-free survival was highly significant (p = 0.0008). Our study shows that postsurgical hyperprolactinemia is associated with a significantly lower recurrence rate and longer disease-free and overall survival in operable node-negative breast cancer patients. Our data suggest that postoperative hyperprolactinemia could be crucial in the development of recurrence in operable breast cancer. Looking at results, the recurrence rate of node-negative patients who did not show postoperative hyperprolactinemia would be, in theory, similar to that of patients with node-positive disease, suggesting that normal postoperative PRL levels could identify a group of node-negative patients at high risk for recurrence.
Background: Despite numerous randomized trials suggesting a benefit of unconventional fractionati... more Background: Despite numerous randomized trials suggesting a benefit of unconventional fractionation in locally advanced head and neck cancer, the role of this approach in nasopharyngeal carcinoma is debatable. Based on the current clinical experience, the authors introduced hyperfractionated irradiation in the treatment of locally advanced head and neck cancer, including nasopharyngeal tumors. The preliminary results of this treatment approach in nasopharyngeal cancer patients are presented, with special focus on the pattern of failure and toxicity. Patients and Methods: 43 patients with nasopharyngeal cancer (stage II–IV, TNM 1997) underwent hyperfractionated irradiation. In 34 cases, radiotherapy was preceded by a median of three cycles of cisplatin-based induction chemotherapy. Irradiation was delivered using a shrinking-field technique up to a total dose of 74.4 Gy in 62 fractions of 1.2 Gy twice daily (minimum 6-h interval)/5 days/week. Results: Acute toxicity of hyperfractionated radiotherapy was significant but tolerable. Mucositis proved the most common side effect (grade 3: 24 patients, grade 4: three patients). Severe late toxicity was not observed. 30 of 34 patients (88%) responded to induction chemotherapy. At 6 weeks after completion of radiotherapy, complete response was seen in 35 patients (81%), partial response in five (12%), stable disease in one, and progressive disease in two. After a median follow-up of 32 months, 18 patients (41%) developed progressive disease. Primary tumor progression was observed in three patients, and seven patients each showed regional lymph node progression and distant metastases. In one case both regional lymph node progression and distant metastases were diagnosed. The 2-year progression-free survival and overall survival rates were 58% and 84%, respectively. Conclusion: Hyperfractionated radiotherapy seems a feasible and active regimen in locally advanced nasopharyngeal carcinoma. Accompanying acute and late toxicity is acceptable and does not compromise delivery of the planned irradiation dose. This regimen is associated with a high local control rate; relatively high nodal and distant failure, however, call for further treatment modifications, e. g., optimization of irradiation technique and/or dose escalation as well as improved systemic therapies. Hintergrund: Obwohl zahlreiche randomisierte Studien zugunsten unkonventioneller Fraktionierungsschemata bei lokal fortgeschrittenenen Kopf-Hals-Tumoren sprechen, ist der Stellenwert dieses Vorgehens beim Nasopharynxkarzinom umstritten. Auf der Basis gängiger klinischer Erfahrung führten die Autoren die hyperfraktionierte Bestrahlung in die Therapie lokal fortgeschrittener Kopf-Hals-Tumoren, einschließlich Nasopharynxkarzinome, ein. Erste Ergebnisse dieses Therapieansatzes bei Patienten mit Nasopharynxkarzinom werden vorgestellt und insbesondere Grenzen des Verfahrens und seine Toxizität diskutiert. Patienten und Methodik: 43 Patienten mit Nasopharynxkarzinom (Stadium II–IV, TNM 1997) erhielten eine hyperfraktionierte Strahlentherapie. In 34 Fällen gingen der Bestrahlung im Mittel drei Zyklen einer Cisplatin-basierten Induktionschemotherapie voraus. Die Strahlentherapie wurde im Rahmen einer „Shrinking-Field-Technik“ bis zu einer Gesamtdosis von 74,4 Gy in 62 Fraktionen mit 2× täglich 1,2 Gy (Minimum 6-h-Interval) an 5 Tagen pro Woche durchgeführt. Ergebnisse: Die Akuttoxizität der hyperfraktionierten Strahlentherapie war bedeutend, aber tolerabel. Häufigste Nebenwirkung war die Mukositis (Grad 3: 24 Patienten, Grad 4: drei Patienten). Schwerwiegende Spättoxizitäten wurden nicht festgestellt. 30 von 34 Patienten (88%) sprachen auf die Induktionschemotherapie an. 6 Wochen nach Abschluss der Strahlentherapie, wurde eine komplette Remission bei 35 Patienten (81%) beobachtet, partielles Ansprechen bei fünf (12%), Krankheitsstillstand bei einem und Fortschreiten der Erkrankung bei zwei Patienten. Nach im Median 32 Monaten Follow-up zeigte sich bei 18 Patienten (41%) eine Progression der Erkrankung. Fortschreiten des Primärtumors wurde bei drei Patienten beobachtet, und sieben Patienten wiesen entweder Befall der regionalen Lymphknoten oder Fernmetastasen auf. In einem Fall wurden sowohl Befall der regionalen Lymphknoten als auch Fernmetastasen diagnostiziert. Das progressionsfreie Überleben und Gesamtüberleben nach 2 Jahren waren 58% bzw. 84%. Schlussfolgerung: Die hyperfraktionierte Strahlentherapie scheint bei lokal fortgeschrittenem Nasopharynxarzinom praktikabel und wirksam zu sein. Die auftretende Akut- und Spättoxizität ist akzeptabel und gefährdet die Verabreichung der geplanten Strahlungsdosis nicht. Dieses Vorgehen führt zu einer hohen lokalen Kontrolle; allerdings verlangt das relativ hohe regionale und systemische Therapieversagen weitere Modifikationen, z. B. die Optimierung der Bestrahlungstechnik und/oder Dosisekalation sowie verbesserte systemische Therapien.
The aim of this study was to assess the potential of perfusion computed tomography (CTp) for moni... more The aim of this study was to assess the potential of perfusion computed tomography (CTp) for monitoring induction chemotherapy in patients with squamous cell carcinoma (SCCA) of the upper aerodigestive tract. Twenty-five patients with advanced SCCA underwent CTp and volumetric CT before and after induction chemotherapy. Perfusion CT parameters were calculated in the tumor, normal tissue, and muscles and correlated with tumor volume. The blood flow (BF), blood volume (BV), and permeability surface were significantly higher, and the mean transit time was significantly lower in the tumor than in the normal tissue. The tumor BF and BV significantly decreased, and the mean transit time significantly increased after the therapy; decrease in BF and BV correlated with tumor volume reduction after chemotherapy. The baseline tumor BV was significantly lower in nonresponders compared with that in responders. In patients with SCCA, CTp showed potential for monitoring induction chemotherapy, reduction in tumor BF and BV correlated with reduction of tumor volume after chemotherapy, and baseline tumor BV may predict response to chemotherapy.
The clinical efficacy and antiangiogenic effect of low-dose, metronomic administration of cycloph... more The clinical efficacy and antiangiogenic effect of low-dose, metronomic administration of cyclophosphamide (CTX) and methotrexate (MTX) (CM) have been demonstrated. The authors report results and long-term follow-up for patients with metastatic breast carcinoma who obtained prolonged clinical benefit with CM. Prospectively collected data from two successive clinical trials were evaluated. From July 1997 to October 2003, patients with metastatic breast carcinoma were treated with low-dose oral chemotherapy (MTX 2.5 mg, twice daily on day 1 and day 2 or 4, and CTX 50 mg daily). Patients who achieved prolonged clinical benefit for a duration of 12 months or more (complete remission, partial remission or stabilization of disease) were considered for the analysis. Median follow-up was 23 months. A total of 153 patients were enrolled and are evaluable: Eastern Cooperative Oncology Group performance status 0-1 in 90 patients, two or more sites of metastatic disease in 97 patients, zero regimen for metastatic breast carcinoma in 48 patients. Among 153 patients, five demonstrated complete remission and 25 partial remission. The proportion of patients who achieved prolonged clinical benefit was 15.7% (95% confidence interval 9.9-21.4%). Median time to progression for patients with prolonged clinical benefit was 21 months (range 12-37+ months). One patient maintained complete remission 42 months after therapy discontinuation. At the multivariate analysis endocrine responsiveness and the achievement of an objective response significantly correlated with the achievement of prolonged clinical benefit. Metronomic chemotherapy can induce prolonged clinical benefit in metastatic breast cancer, supporting its role as an additional therapeutic tool in the treatment of patients with metastatic breast carcinoma.
alpha-Interferon, thalidomide and celecoxib inhibit tumour angiogenesis by differing mechanisms. ... more alpha-Interferon, thalidomide and celecoxib inhibit tumour angiogenesis by differing mechanisms. In a randomized phase II trial to assess tolerability and safety, we assigned patients with advanced slow-growing solid tumours to 1 of 6 two- or three-drug combinations: alpha-interferon 0.5 million IU b.i.d., thalidomide (100 mg b.i.d. reduced to 100 mg daily), or celecoxib (400 mg daily reduced to 200 mg). Circulating endothelial cells and progenitors (CECs, CEPs) and vascular endothelial growth factor were also studied. From January 2002 to September 2005, 62 patients were enrolled. Four months after initiating treatment, 3 (4%) had partial response, 40 (64%) had stable disease and 19 (30%) had disease progression. Median duration of clinical benefit (partial response/stable disease) was 11.3 months. Patients receiving a third drug had significantly less stable disease plus partial response (chi(2) test, p = 0.002) than those receiving two drugs. The treatments were generally well tolerated, but neurotoxicity (G3 lethargy) occurred in 6 patients. Baseline CEPs were lower (p = 0.004) in patients with clinical benefit at 6 months than those without benefit. After 2 months of treatment CECs were lower than at baseline (p = 0.018) in patients without clinical benefit, and CEPs were higher than at baseline (p = 0.003) in patients with benefit. In pretreated patients with advanced slow-growing solid tumours, long-term metronomic administration of two-drug combinations of alpha-interferon, thalidomide or celecoxib was well tolerated and had antitumour activity. Low baseline CEPs in patients with subsequent clinical benefit suggest that CEC count may identify patients likely to benefit from long-term metronomic anti-angiogenic treatment.
Endothelium-journal of Endothelial Cell Research, 2008
High altitude and hypoxia are known to induce polycythemia, pulmonary hypertension, and vascular ... more High altitude and hypoxia are known to induce polycythemia, pulmonary hypertension, and vascular remodeling. The authors investigated a number of blood cell populations in 15 mountain trekkers before and after 12 days spent at &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;3000 m. Red blood cell and platelet count increased, whereas circulating hematopoietic stem cell (enumerated as CD34bright cells), circulating endothelial cell (CEC) and circulating endothelial progenitor (CEP) count significantly decreased. In particular, the authors observed a decrease in the count of viable CECs, and a decrease in the circulating levels of RNA of the endothelial-specific gene VE-cadherin, whereas the fraction of apoptotic/necrotic CECs was stable. These data suggest a unique pattern of modulation of surrogate markers of vascular remodeling induced by exposure to hypobaric hypoxia.
Es una respuesta biológica producida por el organismo como respuesta a determinados estímulos, fu... more Es una respuesta biológica producida por el organismo como respuesta a determinados estímulos, fundamentalmente al estrés. La sonrisa se considera una forma suave y silenciosa de risa.
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