18F-FDG PET/CT impact on testicular tumours clinical management.

PURPOSE: Testicular tumour is the most common malignancy in young men. The diagnostic work-up is mainly based on morphological imaging. The aim of our study was to evaluate the clinical impact of (18)F-FDG PET/CT in patients with testicular tumour. METHODS: We retrospectively evaluated all patients studied by (18)F-FDG PET/CT at our centre. Inclusion criteria were: pathological confirmation of testicular tumour, contrast-enhanced CT scan performed within a month of the PET/CT scan, and clinical/imaging follow-up performed at the Oncology Unit of our hospital. Overall, 56 patients were enrolled and 121 PET/CT scans were evaluated. (18)F-FDG PET/CT was performed following standard procedures and the results were compared with clinical, imaging and follow-up data. Clinicians were contacted to inquire whether the PET/CT scan influenced the patient's management. Answers were scored as follows: start/continue chemotherapy or radiotherapy, indication for surgery of secondary lesions, and clinical surveillance. RESULTS: On a scan basis, 51 seminoma and 70 nonseminoma (NS) cases were reviewed. Of the 121 cases. 32 were found to be true-positive, 74 true-negative, 8 false-positive and 6 false-negative by PET/CT. PET/CT showed good sensitivity and specificity for seminoma lesion detection (92% and 84%, respectively), but its sensitivity was lower for NS forms (sensitivity and specificity 77% and 95%, respectively). The PET/CT scan influenced the clinical management of 47 of 51 seminomas (in 6 chemotherapy was started/continued, in 3 radiotherapy was started/continued, in 2 surgery of secondary lesions was performed, and in 36 clinical surveillance was considered appropriate), and 59 of 70 NS (in 18 therapy/surgery was started/continued, and in 41 clinical surveillance was considered appropriate). CONCLUSION: Our preliminary data demonstrate the potential usefulness of PET/CT for the assessment of patients with testicular tumour. It provides valuable information for the clinical management, particularly for clinical surveillance, post-therapy assessment and when relapse is suspected.

Peritoneal cystic mesothelioma: are surgery and HIPEC optimal first-line treatments?

BACKGROUND: Peritoneal cystic mesothelioma (PCM) is an uncommon clinical pathology. Its high rate of recurrence following partial or total resection as well as its spontaneous onset of malignancy have been well documented in a series of case studies. The medical community has yet to define standardized treatment guidelines for PCM. CASE REPORTS: This study reviews the case of 2 patients admitted and treated for PCM. Recent studies have reported improved recurrence and survival rates achieved by means of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), especially when used as first-line treatments. However, whether or not the use of CRS and HIPEC is more effective than a surgical regimen of multiple debulking procedures, is still the subject of debate. CONCLUSION: CRS and HIPEC as first-line treatments have lower morbidity and mortality rates than regimens of multiple back-to-back surgical procedures, and as such, the CRS/HIPEC method appears to be the more successful approach.

Clinically-staged T3N0 rectal cancer: is preoperative chemoradiotherapy the optimal treatment?

BACKGROUND: Preoperative chemoradiotherapy has been widely adopted as the standard of care for stage II-III rectal cancers. However, patients with T3N0 lesions had been shown to have a better prognosis than other categories of locally advanced tumor. Thus, neoadjuvant chemoradiation is likely to be overtreatment in this subgroup of patients. Nevertheless, the low accuracy rate of preoperative staging techniques for detection of node-negative tumors does not allow to check this hypothesis. We analyzed a group of patients with cT3N0 low rectal cancer who underwent neoadjuvant chemoradiotherapy with the purpose of evaluating the incidence of metastatic nodes in the resected specimens. METHODS: Between January 2002 and February 2008, 100 patients with low rectal cancer underwent clinical staging by means of endorectal ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging. All patients received preoperative 5-fluorouracil-based chemoradiotherapy and surgical resection with curative aim. RESULTS: Of 100 patients with locally advanced rectal cancer, 32 were clinically staged as T3N0M0. Pathological analysis showed the presence of lymph node metastases in nine patients (28%) (node-positive group). In the remaining 23 cases, clinical N stage was confirmed at pathology (node-negative group). Node-positive and node-negative groups differ only in the number of ypT3 tumors (P < .01). CONCLUSIONS: Our results indicate that immediate surgery for patients with cT3N0 rectal cancer represents an undertreatment risk in at least 28% of cases, making necessary the use of postoperative chemoradiotherapy. Preoperative chemoradiotherapy should be the therapy of choice on the grounds of the principle that overtreatment is less hazardous than undertreatment for cT3N0 rectal cancers.

Long-term results of a pilot study on an intensive induction regimen for unresectable stage III non-small-cell lung cancer.

BACKGROUND: In 1995, we designed and carried out a pilot study on the combination of cisplatin + high dose epirubicin + vinorelbine with granulocyte-colony-stimulating factor support for the induction treatment of unresectable stage IIIAN2 and wet IIIB non-small-cell lung cancer. The present report concerns the long-term results. METHOD: Eligible patients received cisplatin, 75 mg/m(2), and epirubicin, 120 mg/m(2), on day 1, vinorelbine, 25 mg/m(2), on days 1 and 15, and granulocyte-colony-stimulating factor, 300 microg s.c., from days 3 to 12. The cycle was repeated every 3 weeks for 3 times. Subsequently, all the patients were re-evaluated for surgical resection. RESULTS: Twenty-six patients were enrolled: 21 males and 5 females; median age, 55 years (range, 31-64); median performance status, 90% (range, 80-100); 16 stage IIIA and 10 IIIB. After the 3 cycles, objective response was as follows: 2 complete (8%), 18 partial (69%), 5 no change (19%) and 1 progressive disease (4%). Ten patients were not operated (9 unresectable and 1 refusal) and received radiotherapy. Sixteen patients (61%) underwent surgery and 14 were completely resected (54%). After a median follow-up of 84 months (range, 12-120), the median overall progression-free survival was 17 months (range, 2-104+): 47 months for resected and 8 months for nonresected patients. The median overall survival was 40 months (range, 4-123+): 87 months for resected and 13 months for nonresected patients. One-year, 3-year and 5-year survival rates were 73%, 42% and 37%, respectively. CONCLUSIONS: These intensive cytotoxic regimen enabled us to obtain favorable long-term results in a selected series of inoperable stage III non-small-cell lung cancer patients.

Multimodal sequential approach in colorectal cancer liver metastases: hepatic resection after yttrium-90 selective internal radiation therapy and cetuximab rescue treatment.

Synchronous or metachronous liver metastases occur in up to one-third of patients with colorectal cancer and are associated with a poor prognosis. Many evidences have shown that surgical resection can be curative, with 5-year survival rates ranging from 37% to 50%, but many patients are ineligible for surgery because of multiple liver lesions, bilobar distribution of liver metastases, or the presence of widespread extrahepatic disease. The management of unresectable liver metastases includes many therapeutic options such as systemic chemotherapy, selective internal radiation therapy (SIRT) with yttrium-90 (Y-90), targeted therapy, and surgery. These treatments can be integrated into a sequential multimodal approach to increase the resection rate. We present a case in which such an approach was put into practice. The favorable result suggests that SIRT, along with systemic chemotherapy and surgery, is a valid treatment option for unresectable colorectal liver metastases.

Does stent placement for advanced colon cancer increase the risk of perforation during bevacizumab-based therapy?

BACKGROUND & AIMS: Data on the safety of bevacizumab-based therapies for patients carrying a self-expandable metallic stent (SEMS) for occlusive colon cancer are lacking. We report 2 cases of colon perforation observed in our case series of patients with SEMS for occlusive colon cancer. METHODS: Patients with occlusive symptoms caused by colon cancer received a colonic stent under endoscopic and radiologic guidance. RESULTS: Over a 10-month period, 28 patients with occlusive colon cancer were treated with stent placement. The stent was placed as a bridge to surgery in 12 patients who were treated surgically within 4 to 78 days after the endoscopic procedures, without any stent-related complications. Seven patients did not receive any other antitumor treatment as a result of concomitant comorbidities. Nine patients with both primary tumor and metastatic lesions were treated with medical therapy. Over a median follow-up period of 131 days colonic perforation occurred in the 2 patients treated with a combination of capecitabine and oxaliplatin plus bevacizumab. CONCLUSIONS: Further studies are needed to clarify whether SEMS placement increases the risk of perforation caused by bevacizumab-based therapies.

Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients: a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group.

PURPOSE: Paclitaxel and carboplatin are frequently used in advanced ovarian cancer following cytoreductive surgery. Threshold models have been used to predict paclitaxel pharmacokinetic-pharmacodynamics, whereas the time above paclitaxel plasma concentration of 0.05 to 0.2 micromol/L (t(C > 0.05-0.2)) predicts neutropenia. The objective of this study was to build a population pharmacokinetic-pharmacodynamic model of paclitaxel/carboplatin in ovarian cancer patients. EXPERIMENTAL DESIGN: One hundred thirty-nine ovarian cancer patients received paclitaxel (175 mg/m(2)) over 3 h followed by carboplatin area under the concentration-time curve 5 mg/mL*min over 30 min. Plasma concentration-time data were measured, and data were processed using nonlinear mixed-effect modeling. Semiphysiologic models with linear or sigmoidal maximum response and threshold models were adapted to the data. RESULTS: One hundred five patients had complete pharmacokinetic and toxicity data. In 34 patients with measurable disease, objective response rate was 76%. Neutrophil and thrombocyte counts were adequately described by an inhibitory linear response model. Paclitaxel t(C > 0.05) was significantly higher in patients with a complete (91.8 h) or partial (76.3 h) response compared with patients with progressive disease (31.5 h; P = 0.02 and 0.05, respectively). Patients with paclitaxel t(C > 0.05) > 61.4 h (mean value) had a longer time to disease progression compared with patients with paclitaxel t(C > 0.05) < 61.4 h (89.0 versus 61.9 weeks; P = 0.05). Paclitaxel t(C > 0.05) was a good predictor for severe neutropenia (P = 0.01), whereas carboplatin exposure (C(max) and area under the concentration-time curve) was the best predictor for thrombocytopenia (P < 10(-4)). CONCLUSIONS: In this group of patients, paclitaxel t(C > 0.05) is a good predictive marker for severe neutropenia and clinical outcome, whereas carboplatin exposure is a good predictive marker for thrombocytopenia.

[Accessibility of home palliative care and place of death of cancer patients: data analysis of the Emilia-Romagna Region.] / Accessibilità di cure palliative domiciliari e luogo del decesso dei malati oncologici: analisi dei dati della Regione Emilia-Romagna.

INTRODUCTION: The ANT Foundation is one of the main non-profit organizations providing palliative care in Italy. For more than 30 years, it has developed a comprehensive home palliative care program for cancer patients predominately active in the Bologna province. One of its main achievements has allowed for the majority of patients to be assisted at home during the last weeks of their lives until time of death. The purpose of the present study is to evaluate the possible impact of the ANT program on health data relating to the location of where cancer patients die within the Local Health Care system area (AUSL) of Bologna, compared to what happens in the other AUSLs of the Emilia-Romagna Region (ERR) where it is not present. METHODS: Regional cancer mortality data in 2005, 2010 and 2015, according to place of death and AUSL, were obtained by consulting the RER database. Data on patients assisted in the same time periods by the ANT program in the Bologna AUSL area were extracted from the ANT Foundation database and analyzed for place of death. RESULTS: In the year 2015, 2965 cancer patients died in the Bologna AUSL area. Compared to other AUSL areas of the ERR, it presents with a lower hospital mortality rate (31.2% vs. 47.5%) and a higher home mortality rate (32.8% vs. 19.6%). On the other hand, in 2015 the ANT program had assisted almost 50% of the total number of cancer patients who died in the Bologna AUSL area. Out of these patients, 64.6% died at home, while only 18.7% and 16.6% died in hospital and hospice, respectively. Conversely, hospital and home mortality rates in patients of the Bologna AUSL area who were not assisted by the ANT program, did approximate the mean values of the other ERR AUSLs. Over the 2005-2015 time span, the home mortality rate in the ANT patient series remained about twice as high as those of the Bologna AUSL. CONCLUSIONS: The comprehensive home palliative care program of the ANT Foundation seems to have a strong impact in determining the reduced hospital mortality rate of the Bologna AUSL area when compared to the other AUSLs of the Emilia-Romagna Region. The extension of this model of comprehensive home-based palliative care to other areas could contribute to reduce the high hospital mortality rate of cancer patients in this Italian Region.

Population pharmacokinetics and pharmacodynamics of doxorubicin and cyclophosphamide in breast cancer patients: a study by the EORTC-PAMM-NDDG.

AIMS: To investigate the population pharmacokinetics and pharmacodynamics of doxorubicin and cyclophosphamide in breast cancer patients. PATIENTS AND METHODS: Sixty-five female patients with early or advanced breast cancer received doxorubicin 60 mg/m(2) over 15 minutes followed by cyclophosphamide 600 mg/m(2) over 15 minutes. The plasma concentration-time data of both drugs were measured, and the relationship between drug pharmacokinetics and neutrophil counts was evaluated using nonlinear mixed-effect modelling. Relationships were explored between drug exposure (the area under the plasma concentration-time curve [AUC]), toxicity and tumour response. RESULTS: Fifty-nine patients had complete pharmacokinetic and toxicity data. In 50 patients with measurable disease, the objective response rate was 60%, with complete responses in 6% of patients. Both doxorubicin and cyclophosphamide pharmacokinetics were associated with neutrophil toxicity. Cyclophosphamide exposure (the AUC) was significantly higher in patients with at least stable disease (n = 44) than in patients with progressive disease (n = 6; 945 micromol . h/L [95% CI 889, 1001] vs 602 micromol . h/L [95% CI 379, 825], p = 0.0002). No such correlation was found for doxorubicin. Body surface area was positively correlated with doxorubicin clearance; AST and patient age were negatively correlated with doxorubicin clearance; creatinine clearance was positively correlated with doxorubicinol clearance; and occasional concurrent use of carbamazepine was positively correlated with cyclophosphamide clearance. CONCLUSIONS: The proposed inhibitory population pharmacokinetic-pharmacodynamic model adequately described individual neutrophil counts after administration of doxorubicin and cyclophosphamide. In this patient population, exposure to cyclophosphamide, as assessed by the AUC, might have been a predictor of the treatment response, whereas exposure to doxorubicin was not. A prospective study should validate cyclophosphamide exposure as a predictive marker for the treatment response and clinical outcome in this patient group.

Cancer chemotherapy near the end of life: the time has come to set guidelines for its appropriate use.

AIMS AND BACKGROUND: This study retrospectively analyzes the use of chemotherapy in patients who died of advanced cancer either after having been in care at the Medical Oncology Unit (MOU) of the University Hospital of Bologna, Italy, or after having been assisted in their terminal disease phase by the Bologna Oncological Hospice at Home (OHH) of the Associazione Nazionale Tumori (ANT) Italia Foundation. In the latter group, the prescription and delivery of chemotherapy had been performed by doctors of medical oncology departments other than the MOU. RESULTS: Between January 2003 and September 2005, 793 deaths of patients were recorded (MOU: 312; OHH: 481). At least one cycle of chemotherapy had been received by 445 patients (56.1%). The most common cancer types were lung cancer (26.7%), colorectal cancer (14.8%), and breast cancer (11.2%). At the time of the last chemotherapy (I-CT), the median age of the patients was 68 years (range, 22-98 years) and the median KPS was 70 (range, 40-100). The median interval between I-CT and death was 71 days (range, 1-1913 days). One hundred and one patients (22.7%) had received their I-CT in the last 30 days of their life, 86% of them having intermediately chemosensitive (71%) or chemoresistant (14%) tumors. The I-CT in the last month of life was first line in 56% of cases and consisted of costly new-generation drugs in 36.6% of cases. CONCLUSIONS: The study suggests the urgent need to lay down guidelines for the appropriate use of chemotherapy in advanced cancer patients with a short life expectancy.

18FDG-PET evaluation correlates better than CT with pathological response in a metastatic colon cancer patient treated with bevacizumab-based therapy.

Around 20-30% of patients with hepatic metastasis from colorectal cancer can undergo liver resection, but the increased response rate obtained with the addition of monoclonal antibodies to chemotherapy regimens could result in a higher rate of liver surgery. In this report we describe the case of a patient who underwent a liver resection after neoadjuvant treatment with capecitabine, oxaliplatin and bevacizumab and who achieved a complete pathological response of the liver metastasis. A preoperative CT scan demonstrated a partial response to the treatment while 18FDG-PET scan correctly evaluated the complete pathological response in the liver and detected an active interaortocaval lymph node metastasis. New specific studies are required to evaluate the imaging response in metastatic colorectal cancer patients especially after treatment with new, targeted agents.

Impact of intervention aimed at improving the integration of oncology units and local palliative care services: results of the multicentre prospective sequential MIRTO study.

BACKGROUND: Chemotherapy (CT) in patients with advanced cancer (ACP) near the end of life is an increasing practice of oncology units. A closer integration with palliative care (PC) services could reduce the use of potentially harmful CT. This prospective study is aimed at assessing whether a more integrated care model could reduce CT use near the end of life and increase local PC service utilisation. METHODS: The study enrolled sequentially two cohorts of ACP with an estimated life expectancy of ≤6 months. In the first cohort, the usual oncologist's practice to prescribe CT and to activate local PC services were recorded. In cohort 2, the oncologist's decision was taken after an in-hospital consultation with the local PC teams. After patient death, a follow-back survey was carried out. RESULTS: The two cohorts included 109 and 125 evaluable patients, respectively. The oncologist's decision to prescribe CT occurred in 51.4% and 60%, respectively: the percentages of patients receiving the final CT administration in the last 30 days of life did not differ in the two cohorts (33.9% and 29.3%, respectively,p=0.83). Conversely, an increase in home PC service utilisation (from 56.9% to 82.4%, p=0.00), at home deaths (from 40.4% to 56.8%, p=0.01) and in-hospice deaths (from 8.3% to 19.2%, p=0.00) occurred in cohort 2. CONCLUSION: The implementation of an initial in-hospital consultation of oncologists and experienced home PC teams has not reduced the use of CT near the end of life but increased PC service utilisation and reduced in-hospital deaths.

Capecitabine plus oxaliplatin (xelox) versus protracted 5-fluorouracil venous infusion plus oxaliplatin (pvifox) as first-line treatment in advanced colorectal cancer: a GOAM phase II randomised study (FOCA trial).

UNLABELLED: This phase II randomised trial compares oxaliplatin plus protracted infusion of 5-fluorouracil (pviFOX) or oxaliplatin plus capecitabine (XELOX) in the first-line treatment of advanced colorectal cancer (ACRC). METHODS: From December 2001 to March 2005, 118 patients were randomised to arm A (pviFOX: pvi5-FU by a central venous catheter 250 mg/m2/daily d1-21+oxaliplatin 130 mg/m2 d1 q3w) (56 pts) or arm B (XELOX: capecitabine 1000 mg/m2 po bid d1-14+oxaliplatin at the same schedule) (62 pts). RESULTS: Patient characteristics were well-balanced between the two arms. Median number of complete cycles was six. The objective responses were: CR 1 (1.7%) and 3 (4.8%), PR 26 (46.4 %) and 24 (38.7%), SD 13 (23.2%) and 20 (32.3%), P 13(23.2%) and 10 (16.1%), not evaluable 3 (5.4%) and 5 (8.1 %) in arms A and B, respectively; the CR+PR rate was 48.2% (95% confidence limits 34.6%-61.9%) versus 43.5 % (31.0%-56.7%). Median TTP was 7 versus 9 months, respectively. About 50% of the patients with symptoms or low performance status at baseline experienced improvement without major differences between the two arms. G3-4 diarrhoea was observed in 14.0% versus 8.2%, G3 stomatitis in 3.7% versus 0, and G3 neurotoxicity in 18.5% versus 24.6% in arms A and B, respectively. Eight patients in arm A (14.8%) had venous line problems that obliged the temporary suspension (six cases) or stopping (two cases) of the 5-FU infusion. CONCLUSION: Both pviFOX and XELOX are effective and safe first-line treatments for patients with ACRC. By avoiding intravenous (i.v.) administration by a central catheter, XELOX is favoured in clinical practice.

Sequential chemotherapy with cisplatin/gemcitabine (CG) followed by mitoxantrone/methotrexate/mitomycin (MMM) in patients with malignant pleural mesothelioma. A multicenter Italian Phase II Study (SITMP1).

PURPOSE: We performed a multicenter phase II trial to evaluate the impact on the activity, efficacy, symptom control and safety of using two active regimens in a sequential schedule (cisplatin/gemcitabine followed by mitoxantrone/methotrexate/mitomycin) as first-line chemotherapy for unresectable malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: A total of 54 patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1,200 mg/m(2) on days 1 and 8, every 3 weeks for four courses (CG regimen) followed by mitoxantrone 10 mg/m(2) on day 1, methotrexate 35 mg/m(2) on day 1 and mitomycin 7 mg/m(2) on day 1, every 3 weeks with mitomycin in alternate cycles for four courses (MMM regimen). RESULTS: We observed 3 complete responses (CRs) (5.6%) and 13 partial responses (PRs) (24.0%), with an overall response rate (ORR) of 29.6% (95% confidence interval, 17-42%), 33 stable disease (SD) (61.1%) and 5 progressive disease (PD) (9.2%). Median time to progression (TTP) was 9.5 months (range, 2-23). Median overall survival (OS) was 13 months (range, 3-33); 1-year survival rate was 63%. The treatment produced a good symptom control, with an improvement during chemotherapy in dyspnea and pain in 52.9 and 48.3% of patients, respectively. The major toxicity observed was hematological. Grades 3-4 NCI-CTC v 2.0 toxicity with the CG regimen included: neutropenia (11.1%), anemia (1.9%), thrombocytopenia (7.4%), vomiting (11.1%) and with the MMM regimen: neutropenia (35.2%), anemia (5.5%), thrombocytopenia (7.4%) and stomatitis (1.9%). CONCLUSION: This phase II study with the sequential approach of two active regimens showed a good disease control in MPM, with symptom improvement and only mild toxicity.

Does biomolecular characterization of stage II/III colorectal cancer have any prognostic value?

As new improvements in the treatment of colorectal cancer have become available, it has become important to understand the benefits of new therapies or the deleterious effects stemming from the increased risk of toxicity. In particular, a more rational approach to adjuvant chemotherapy for patients with stage II/III disease should be defined by understanding which patients have a higher recurrence risk. Many studies have investigated several molecular markers, but none has been definitively associated with patient outcome. We present a review of studies that have evaluated the immunohistochemical correlation between expression of some biomarkers, such as thymidylate synthase, p53, Ki-67, Bcl-2, and microsatellite instability status expressed by Mut-L homologue 1 and Mut-S homologue 2 proteins, and the prognosis of patients with stage II/III colorectal cancer. We have evaluated studies in which > or = 100 patients were involved in an effort to ensure a representative study group. The only biomarker likely to have a prognostic value is microsatellite instability status, which correlated with a better prognosis.

Trastuzumab plus estrogen suppression as salvage treatment in a case of liver failure due to metastatic breast cancer.

BACKGROUND: Liver failure associated with metastatic breast cancer is a short-term survival condition in which standard chemotherapy is almost always contraindicated. CASE REPORT: A 45-year-old premenopausal woman with jaundice, due to extensive metastatic liver involvement from infiltrating ductal carcinoma of the right breast, with positive hormonal receptors (ER 70%, PgR 80%), a high proliferative index (Ki-67 60%) and HER2 overexpressed (immunohistochemical HercepTest 3+) was referred. Metastases were also present in the lymph nodes of the homolateral axilla and in both lungs (T2N2M1). Liver function indices were quite altered, in particular: total bilirubin 12.32 mg/dl (direct 11.49 mg/dl), ammonemia 270 microMoles/l and albumin 2.9 g/dl. Treatment consisted of trastuzumab at a loading dose of 4 mg/kg, followed by weekly doses of 2 mg/kg, Leuprolide at 3.75 mg intramuscularly monthly and Tamoxifen 20 mg daily. RESULTS: The patient presented a rapid and progressive improvement in her clinical conditions and in liver tests. The jaundice was resolved after 1.5 months and after 4 months she had normal liver function tests and an objective partial response was evident. The treatment was optimally tolerated. At this point Taxol, at a dose of 80 mg/m2 weekly, was added. After 10 months, the patient was well with a very important objective remission of all the tumor masses, and is continuing with the combined treatment. CONCLUSION: Trastuzumab plus estrogen suppression can be an effective salvage therapy in patients with liver failure due to metastatic HER2 and ER/PgR-positive breast cancer.

Planned sequence of gemcitabine followed by vinorelbine in the treatment of elderly patients with advanced non-small cell lung cancer.

BACKGROUND: The rationale for planned sequential chemotherapy is based on the principle that sequential administration of non-cross-resistant cytotoxic agents has the advantage of eliminating additive toxicity and permitting the delivery of full doses of each drug. At present, there is a lack of data on the results of planned sequential single agent administration in elderly patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to explore the possibility of increasing the time-to-progression (TTP) by a 1.5 factor in comparison with the historical results of monochemotherapy with a first-line planned sequential administration of gemcitabine (GEM) and vinorelbine (VNR). PATIENTS AND METHODS: GEM 1000 mg/m2 was administered intravenously (i.v.) for 30 min on days 1, 8 and 15 and recycled on day 28 for a total of 3 cycles. Independently of response, VNR was administered i.v. as a bolus at a dose of 25 mg/m2 on days 1, 8 and 15 of a 28-day cycle. VNR treatment was continued until disease progression or intolerance. RESULTS: Fifty-two consecutive patients, with a median age of 76 years (70-85), affected by locally advanced (35%), metastatic (54%) or recurrent (11%) NSCLC were enrolled. The overall best objective response was 3.8% CR, 19.2% PR, 32.7% SD, 23.1% disease progression and 21.2% not evaluable. Both drugs were well tolerated. The median TTP was 6 months (95% confidence limits 4-8), the median overall survival was 10 months (95% confidence limits 6-14) and the one-year survival rate was 42%. CONCLUSION: The planned sequential administration of GEM and VNR suggests that the TTP can be increased with the use of the 2 single agents in elderly patients with locally advanced or metastatic NSCLC.

Gemcitabine plus mitoxantrone and prednisone in the palliative treatment of hormone-resistant prostate cancer (HRPC): A phase II study (GOAM 01.01 study).

BACKGROUND: The present exploratory phase II study was performed to evaluate the activity and tolerability of adding a second agent (gemcitabine) to the well-tolerated mitoxantrone/prednisone regimen in patients with locally advanced or metastatic prostate cancer no longer responsive to hormonal treatment. PATIENTS AND METHODS: Forty-three patients with hormone-refractory prostate cancer (HRPC) were included in the study from May 2000 to April 2004. Their median age was 71 years (range, 56-81) and their median Karnofsky performance status (KPS) was 90 (range, 70-100). The treatment schedule consisted of intravenous (i.v.) mitoxantrone (8 mg/m2 on day 1), i.v. gemcitabine 800 mg/m2 on days 1 and 8, recycled every 21 days and oral prednisone administered at a dose of 10 mg per day. Hormonal treatment with LHRH was continued in all patients. Up to six cycles of treatment were planned in the absence of progressive disease. RESULTS: Sixteen patients had measurable disease (six patients only measurable disease, ten patients bone disease plus measurable disease) and 27 patients had only bone disease. Concerning the PSA levels, a partial response (PR) was observed in 15 patients (38%), stable disease (SD) in 16 patients (41%) and progressive disease (PD) in eight patients (21%). The objective response was evaluable in 16 patients; one patient was not evaluable because he had received only one cycle. Ten patients (63%) had SD and five patients (31%) PD. In the ten evaluable patients with objective SD, depending upon the PSA response, three PR, six SD and one PD were observed. Among the five patients who progressed, three PD and two SD were observed as a PSA response. Pain remission was recorded in 15/41 patients (36%) and the KPS remained stable in most patients. The median overall survival was 15 months (range, 1-41) (95% CI: 10-20 months). The 1-year survival rate was 61%. Hematological toxicity was mild: G 3-4 neutropenia was observed in five (12%) patients. There were no neutropenic, fevers. No significant non-hematological toxicity was observed. CONCLUSION: The mitoxantrone, gemcitabine and prednisone combination, in accordance with the present regimen, was feasible, had a palliative effect, good tolerance and antitumor activity. Nonetheless, our results do not seem to be superior to those previously described for mitoxantrone plus prednisone.

Pharmacokinetics of third-generation aromatase inhibitors.

The latest generation of nonsteroidal aromatase inhibitors (anastrozole and letrozole) has been approved by the US Food and Drug Administration for use in the first- and second-line treatment of postmenopausal women with hormone receptor-positive (or unknown) breast cancer. The steroidal agent exemestane is approved for second-line treatment and is currently being evaluated for first line. In addition, these agents are being evaluated in the adjuvant and neoadjuvant settings. Because preclinical studies have suggested some differences in the efficacy of these agents to inhibit aromatase, it has been important to evaluate whether these properties actually translate into meaningful differences in the clinical setting. The pharmacokinetic properties of each aromatase inhibitor influences their ability to perform effectively. Examination of the data suggests differences in uptake rates, half-life of elimination, metabolism, and clearance rates that could influence their efficacy. However, the significance of these differences for clinical effectiveness over long-term use remains to be determined.