Patients with cancer and hospital admissions: disease trajectory and strategic choices.

OBJECTIVES: Hospital admission (HA) in cancer history is a common, repeated and frequently unplanned event. The emergency departments (EDs) and the oncological outpatient service (OOS) are the ordinary way of entry. We studied the reasons of admission, pathways of access and discharge and prognostic factors in a population of admitted patients with cancer. METHODS: The health records of the admitted patients in the oncological ward of a referral hospital in a 6-month period were retrieved and analysed. The characteristics of those admitted in the last 3 months of life were compared with the other group. RESULTS: Among the 147 HA, 79.5% were unplanned, 48.9% passing through the ED and 30.6% through the OOS; 56.5% were due to cancer-related symptoms; 50.3% occurred in the last 3 months of life. Median overall survival was 90 days (95% IC 53.1-126.9). Independent prognostic factors for survival were: being admitted for symptoms, referral through the ED and not being discharged at home. CONCLUSIONS: Hospital is a turning point in the cancer care pathway. Patients needing HA have a dismal prognosis, half of them being in the last 3 months of life. This group can be identified using universally available variables.

A phase II, open-label, single-arm trial of carboplatin plus etoposide with bevacizumab and atezolizumab in patients with extended-stage small-cell lung cancer (CeLEBrATE study): background, design and rationale.

Based on improved survival from the addition of PD-L1 inhibitors in phase III trials, the combination of immunotherapy and platinum-doublet chemotherapy has become the new standard treatment for extended-stage small-cell lung cancer (ES-SCLC). Furthermore, the antiangiogenetic agent bevacizumab showed a longer progression-free survival by targeting VEGF that has pleiotropic effects, including immunosuppressive ones. We, therefore, hypothesized that targeting angiogenesis would improve the efficacy of chemoimmunotherapy. The CeLEBrATE trial is an open-label, multicenter, phase II study designed to assess the efficacy and safety of the combination of carboplatin and etoposide plus bevacizumab and atezolizumab in treatment-naive patients with ES-SCLC. The primary end point is overall survival rate at 1 year, while secondary end points include overall response rate, progression-free survival and toxicity.

Lay abstract Extended-stage small-cell lung cancer (ES-SCLC) is a highly aggressive lung cancer subtype, accounting for 13­15% of all lung cancers. For several years, the standard treatment for this disease was based on polychemotherapy, with a rapid disease response but with an equally rapid disease progression. The new standard treatment has recently been changed, based on the results of two large clinical trials, which showed the efficacy and safety of the combination of chemotherapy with immunotherapy compared to chemotherapy alone. Nevertheless, prognosis of ES-SCLC remains poor, and new treatment strategies are urgently needed. Therefore, we designed the CeLEBrATE trial to investigate whether the combination of chemotherapy with antiangiogenetic therapy and immunotherapy is safe and could improve survival in patients with ES-SCLC.

Molecular profiling of advanced non-small cell lung cancer in the era of immunotherapy approach: a multicenter Italian observational prospective study of biomarker screening in daily clinical practice.

AIMS: Heterogeneous implementation of molecular tests in current diagnostic algorithm at a European and international level is emerging as a major issue for efficient lung cancer molecular profiling. METHODS: From May 2017 until October 2017, N=1612 patients referring to 13 Italian institutions were selected, at advanced stage non-small cell lung cancer (NSCLC), and prospectively evaluated. Principal endpoints were: the percentage of diagnoses performed on cytological and histological material, the proportion of requests for epidermal growth factor receptor (EGFR) mutational status, and resistance mutations detected on tissue and/or liquid biopsy samples after first-generation or second-generation tyrosine kinase inhibitors, the proportion of requests for anaplastic lymphoma kinase (ALK) gene rearrangements, ROS proto-oncogene 1 (ROS1) and Kirsten Rat Sarcoma (KRAS) determinations, the proportion of requests for programmed death-ligand1 (PD-L1) evaluation and, finally, the different assays used for the detection of EGFR mutations, ALK and ROS1 gene rearrangements and PD-L1 expression. RESULTS: Of 1325 patients finally included, only 50.8% requests were related to driver mutations with target agents already available in first-line at that preplanned time, while 49.2% were associated with PD-L1, ROS1, KRAS and others. Multiplex genomic assays (such as next-generation sequencing) were considered by all participating centres. CONCLUSIONS: To the best of our knowledge, this is the first study in a 'real-life daily practice' involving both pathologists and oncologists evaluating routinely workflow and trends towards improvements in molecular requests. Collected data aim to describe the applied algorithms and evolution of molecular screening for stage IV NSCLC in clinical practice.

Atezolizumab in a CoHort of pretreated, advanced, non-small cell lung cancer patients with rare HistologiCal SubtypEs (CHANCE trial).

BACKGROUND: Although immunotherapy with immune-checkpoint inhibitors (ICIs) has profoundly changed the therapeutic scenario in the treatment of advanced non-small cell lung cancer (NSCLC), trials of ICIs only enrolled NSCLC patients with common histology. Atezolizumab was approved by the United States Food and Drug Administration (US FDA) in October 2016 and by the European Medicines Agency (EMA) in September 2017 for the treatment of patients with metastatic NSCLC whose disease progressed during or following platinum-containing chemotherapy, regardless of PD-L1 expression. METHODS: We designed a single-arm, multicenter, two-stage phase II study and plan to enroll 43 patients. The primary objective of the study is to evaluate the antitumor activity of atezolizumab in advanced NSCLC patients with rare histology subtypes. Patients with prior atezolizumab or ICI treatment and with untreated, symptomatic, or progressing brain metastases will be excluded. The primary endpoint is disease control rate. Secondary objectives are toxicity and safety, overall response rate, progression-free survival, overall survival, and time to progression. Diagnosis of NSCLC with rare histology will be confirmed by central pathology revision, and will include: colloid carcinoma, fetal adenocarcinoma, non-endocrine large cell carcinoma, sarcomatoid carcinoma, salivary gland-type tumor, lymphoepithelioma-like carcinoma, and NUT-nuclear protein in testis carcinoma. Archival tumor tissue is required for correlative studies of PD-L1 expression on tumor cells and tumor infiltrating lymphocytes. CONCLUSIONS: Therapeutic options in NSCLC with rare histology subtypes, to be assessed in specifically designed trials, are an unmet need. This trial will help elucidate the role of atezolizumab as a viable option in this setting.

Treating patients with cancer amidst the COVID-19 pandemic: experience of a regional hospital in the Piedmont region in northern Italy.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is posing an unprecedented dilemma to oncologists worldwide, forcing them to decide whether to continue or suspend treatments in order to protect their most vulnerable patients from infection. After the first report from China, the outbreak spread rapidly worldwide. To, date no clear indications on how to treat patients with cancer with COVID-19 infection are available. METHODS: We report data on 21 patients with cancer referred to a single medical oncology unit of a general hospital from mid-March to April 23, 2020. RESULTS: Nine patients were on active cancer therapy during the infection and all stopped medical treatments. Overall 8 patients developed pneumonia and 6 patients died of COVID-19. CONCLUSION: The management of patients with cancer during the pandemic should be carefully balanced and discussed among oncologists and other key professionals involved in the treatment of this vulnerable group of patients, in order to balance the risk of treatment and the risk of infection.

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL).

BACKGROUND: Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC. METHODS: In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). RESULTS: Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months). CONCLUSIONS: Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met. CLINICAL TRIAL REGISTRATION: Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762.

Final results of the SENECA (SEcond line NintEdanib in non-small cell lung CAncer) trial.

OBJECTIVES: Despite the scant docetaxel's tolerability, second-line association with nintedanib still represents a standard-of-care for non-squamous non-small cell lung cancer (nsNSCLC), giving to rapidly-progressing patients the greatest survival advantage. The SENECA trial is a phase IIb, open-label, study evaluating whether nintedanib/docetaxel can be equally effective and safe regardless docetaxel schedule. MATERIALS AND METHODS: Recurrent nsNSCLC patients were stratified into cohort 1 and 2, according to relapse-time (within or over 3 months) from end of first-line chemotherapy. They were treated with docetaxel (T1: 33 mg/mq on days 1 and 8 in a 21-days cycle; T2: 75 mg/mq q3wks) plus nintedanib, allowing maintenance in case of disease-control. Primary endpoint was progression-free survival (PFS) by investigator's assessment; secondary endpoints: overall survival (OS), safety and quality-of-life. RESULTS: Between January 2016-April 2018, 212 patients were evaluated: 30 resulted screening-failures, 12 were excluded for lack of compliance. According to investigator's choice, 85 patients received T1 docetaxel and 85 T2; 138 (81.2%) were stratified in C1, 32 (18.8%) in C2, with a median relapse-time of 0.54 and 9.29 months, respectively. Baseline characteristics were balanced between groups. After 35.5 months follow-up, no survival differences appear between cohorts and treatments; toxicity seems to be slightly higher in T2, especially for chemotherapy-related events. Perception of quality-of-life remains stable and docetaxel schedule doesn't modify patients' load. CONCLUSION: The SENECA trial confirms efficacy of second-line nintedanib/docetaxel for nsNSCLC, regardless time of recurrence and docetaxel schedule; higher toxicities for q3wks docetaxel, without alterations in quality-of-life, have been described, underling the possibility, adopting the weekly schedule, to maintain efficacy with better tolerability.

Prolonged Drainage and Intrapericardial Bleomycin Administration for Cardiac Tamponade Secondary to Cancer-Related Pericardial Effusion.

Malignant pericardial effusion (MPE) is a serious complication of several cancers. The most commonly involved solid tumors are lung and breast cancer. MPE can give rise to the clinical picture of cardiac tamponade, a life threatening condition that needs immediate drainage. While simple pericardiocentesis allows resolution of the symptoms, MPE frequently relapses unless further procedures are performed. Prolonged drainage, talcage with antineoplastic agents, or surgical creation of a pleuro-pericardial window are the most commonly suggested ones. They all result in MPE resolution and high rates of long-term control. Patients suitable for further systemic treatments can have a good prognosis irrespective of the pericardial site of disease. We prospectively enrolled patients with cardiac tamponade treated with prolonged drainage associated with Bleomycin administration. Twenty-two consecutive patients with MPE and associated signs of hemodynamical compromise underwent prolonged drainage and subsequent Bleomycin administration. After injection of 100 mg lidocaine hydrochloride, 10 mg Bleomycin was injected into the pericardial space. The catheter was clumped for 48 h and then reopened. Removal was performed when the drainage volume was <25 mL daily. Twelve patients (54%) achieved complete response and 9 (41%) a partial response. Only 1 (5%) had a treatment failure and underwent a successful surgical procedure. Acute toxicity was of a low degree and occurred in 7 patients (32%). It consisted mainly in thoracic pain and supraventricular arrhythmia. The 1-year pericardial effusion progression-free survival rate was 74.0% (95% confidence interval [CI]: 51.0-97.3). At a median follow-up of 75 months, a pericardial progression was detected in 4 patients (18%). One- and two-year overall survival rates were 33.9% (95% CI: 13.6-54.2) and 14.5% (95% CI: 0.0-29.5), respectively, with lung cancer patients having a shorter survival than breast cancer patients. The worst prognosis, however, was shown in patients not suitable for systemic treatments, irrespective of the site of the primary tumor.Prolonged drainage and intrapericardial Bleomycin is a safe and effective treatment, which should be considered as first choice at least in patients suitable for active systemic treatment.

Pemetrexed versus pemetrexed and carboplatin as second-line chemotherapy in advanced non-small-cell lung cancer: results of the GOIRC 02-2006 randomized phase II study and pooled analysis with the NVALT7 trial.

PURPOSE: To compare efficacy of pemetrexed versus pemetrexed plus carboplatin in pretreated patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC, in progression during or after first-line platinum-based chemotherapy, were randomly assigned to receive pemetrexed (arm A) or pemetrexed plus carboplatin (arm B). Primary end point was progression-free survival (PFS). A preplanned pooled analysis of the results of this study with those of the NVALT7 study was carried out to assess the impact of carboplatin added to pemetrexed in terms of overall survival (OS). RESULTS: From July 2007 to October 2009, 239 patients (arm A, n = 120; arm B, n = 119) were enrolled. Median PFS was 3.6 months for arm A versus 3.5 months for arm B (hazard ratio [HR], 1.05; 95% CI, 0.81 to 1.36; P = .706). No statistically significant differences in response rate, OS, or toxicity were observed. A total of 479 patients were included in the pooled analysis. OS was not improved by the addition of carboplatin to pemetrexed (HR, 90; 95% CI, 0.74 to 1.10; P = .316; P heterogeneity = .495). In the subgroup analyses, the addition of carboplatin to pemetrexed in patients with squamous tumors led to a statistically significant improvement in OS from 5.4 to 9 months (adjusted HR, 0.58; 95% CI, 0.37 to 0.91; P interaction test = .039). CONCLUSION: Second-line treatment of advanced NSCLC with pemetrexed plus carboplatin does not improve survival outcomes as compared with single-agent pemetrexed. The benefit observed with carboplatin addition in squamous tumors may warrant further investigation.

Impact of age on acute toxicity induced by bio- or chemo-radiotherapy in patients with head and neck cancer.

INTRODUCTION: The purpose of this study is to retrospectively analyze acute toxicity encountered in young and old patients treated with chemo-radiation or bio-radiation at the S. Croce General Hospital between 1997 and 2008, in daily clinical practice. MATERIAL AND METHODS: Three hundred and seventeen patients were allocated into two groups according to age (cut-off 65 years). The two groups were compared in terms of treatment related toxicities, treatment activity and efficacy. Epidermal Growth factor receptor (EGFr), Human papillomavirus (HPV) and p53 status were also considered. RESULTS: As expected, overall survival was significantly worse in elderly patients (p=0.005), but response rate, including complete response rate, was similar between the two age groups, as were most of the side effects analyzed. However, infections (p=0.011) and in particular pneumonias (p=0.002) were significantly more represented in elderly patients. CONCLUSION: Elderly patients treated with chemo-radiation or bio-radiation in our centre had a higher risk of infection and in particular, pneumonia. These data suggest a more careful follow-up, but age alone does not justify their exclusion from treatment.

MDM2 309 polymorphism predicts outcome in platinum-treated locally advanced head and neck cancer.

Chemo-radiotherapy (CRT) with cisplatin-based regimens is curative in a subset of patients with locally advanced (stage III and IV) squamous carcinomas of the head and neck (LAHNSCC), but causes considerable toxicity. To seek predictive biomarkers, we analysed single nucleotide polymorphisms (SNPs) in the p53 and MDM2 genes in LAHNSCC patients treated with cisplatin-based CRT. We analysed germ-line p53 72 Arg/Pro (R/P) and MDM2 309 SNPs and somatic p53 mutational status in 140 LAHNSCC and determined their utility as predictive biomarkers. In cases with wild-type p53, overall survival (OS) was longest in 72RR (median OS=60.8 months) and less favourable in 72PP (median OS=6.7 months, p<0.0001). OS in individuals with 72RP was intermediate between 72RR and 72PP, while in patients with missense p53 mutations, median OS did not reach statistical significance. Median OS was significantly shorter in patients with MDM2 309 SNP genotypes GG or GT, compared to TT (15 vs. 86 months; p<0.0001). The predictive effect of the G allele was maintained independent of age, gender, stage, primary site, nodal status, performance status, EGFR grade, HPV status, p53 mutation and p53 SNP (HR for death 3.241; 95% CI 1.90-5.52, p<0.001). The predictive utility of the MDM2 germ-line 309 SNP, which can be easily determined from peripheral blood, implies that it may be of value in the objective selection of patients for radical CRT. In contrast, the predictive utility of the 72 Arg/Pro SNP in p53 requires mutational analysis of p53, limiting its routine clinical use.

The effects on pain and activity of daily living caused by crusted exudation in patients with head and neck cancer treated with cetuximab and radiotherapy.

PURPOSE: To date, the specific role of "in-field" crusting exudation on pain and on activity of daily living (ADL) in head and neck cancer (HNSCC) patients undergoing treatment with cetuximab and radiochemotherapy has been neglected. The purpose of the study was to evaluate the role of crusting exudation on the severity of pain and ADL METHODS: Thirty-seven of the 45 HNSCC patients enrolled in the alternating radiotherapy, chemotherapy, and cetuximab trial were evaluated in this study. The main radiodermatitis signs (the intensity of erythema, the extension of dry, and moist desquamation and of necrosis)--including crusting exudation severity--pain, ADL, and radiodermatitis scores were registered at least weekly during and after treatment. The correlation between crusting exudation and pain or ADL was evaluated. RESULTS: The "in-field" crusting exudation score seemed to have the strongest correlation with pain (Spearman's rho = 0.897; p < 0.001) and the most intense influence on it (Co-B = 0.715; 95% C.I. = 0.643-0.787). However, it seemed to have a weaker correlation with ADL than the other clinical radiodermatitis signs. CONCLUSIONS: Crusts have the strongest correlation with pain in patients with Cetuximab-related radiation dermatitis. Moreover, the presence of crusts can lead operators to misclassify dermatitis as score 4, causing unnecessary delays or interruptions in treatment.

Postoperative therapy in head and neck cancer: state of the art, risk subset, prognosis and unsolved questions.

Head and neck cancer may be easily controlled at early stages, but resectable locally advanced disease often relapses at T and N sites. Therefore, adequate adjuvant treatment is of crucial importance for improving local control and/or survival. Unfortunately, little data are available on the adjuvant setting. Adjuvant radiotherapy is regarded as a standard approach for patients with locally advanced radically resected head and neck cancer, while postoperative chemotherapy alone cannot be considered outside of clinical trials. However, chemoradiotherapy is widely considered superior to radiotherapy in patients at a high risk of relapse and may be considered the standard treatment in this population. In this respect, in the last few decades, there has been a growing interest due to the emerging data on both tumor biology and clinical trials. Several pathological and molecular factors, affecting behavior and head and neck cancer prognosis, could allow for a better selection of postoperative treatment. More recently, new prognostic and predictive factors were identified, including biomolecular aspects, human papillomavirus infection and lifestyle. The integration of these new factors deserves dedicated clinical studies, but the available knowledge already allows some deductive hypotheses. We performed a review of the literature to analyze the role of therapy in the postoperative setting and to discuss both the possibility of a different approach to each class of risk and the unsolved question for which randomized trials are warranted.

Survival prediction and frequency of anticancer treatment in cancer patients hospitalized due to acute conditions. Role of clinical parameters and PaP score.

PURPOSE: Survival prediction is useful in selecting patients for palliative care or active anticancer therapy. The palliative and prognostic (PaP) score was shown to predict 1-month survival in terminally ill patients. Its application to patients with less advanced disease is a subject of debate. We assessed the value of the PaP score and of other clinical parameters in predicting survival in patients admitted in an oncological ward due to acute conditions. We also evaluated the frequency of active anticancer treatment in the last weeks of life. METHODS: All the 208 patients, consecutively admitted in a department of medical oncology and radiotherapy in a 9-month period, were included. Patients and disease features together with the PaP score were assessed and included in a multivariable model for survival prediction. RESULTS: Overall, median survival was 19 weeks and 12-week survival was 59.6%. The PaP score accurately predicted 4-week survival. Among the 39 patients who died within 4 weeks, 36% were on active treatment. The reason of admission, disease control, treatment, and PaP score were independently related to 12-week survival in the multivariate analysis; however patients with a 12-week survival lower than 30% were a minority. CONCLUSIONS: Although the PaP score accurately predicts life expectancy, its use in the setting of acute conditions seems not straightforward, due to the overall good prognosis of these patients. Active treatment in the last period of life is common. The potential reversibility of acute conditions makes prognostic measures inadequate for the purpose of treatment choices.

EGFR status and prognosis of patients with locally advanced head and neck cancer treated with chemoradiotherapy.

BACKGROUND: Overexpression of epidermal growth factor receptor (EGFR) is related to poor prognosis in patients with head and neck cancer (HNC) treated with surgery or radiotherapy. We assessed the relationship between EGFR status and outcome in patients treated with concurrent chemoradiotherapy. PATIENTS AND METHODS: Among 149 patients with unresectable HNC treated with chemoradiotherapy, immunohistochemistry was performed on 122 available tumor specimens. The following factors were included in the analysis: age at diagnosis, gender, performance status, site of primary tumor, T- and N-stage, grading, pretreatment, treatment protocol and EGFR staining. RESULTS: Overall, 43/122 (35%) were considered positive. At a median follow-up of 45 months, 5-year survival did not differ between positive and negative cases (42.1% vs. 48.0% respectively: hazard ratio for death 1.23; 95% confidence interval 0.70 to 2.17, p=0.45) nor was 5-year progression-free survival and 5-year locoregional control. Only when a smaller subgroup of tumors showing the strongest EGFR expression was considered, was any difference in 5-year overall survival detected (33.6% vs. 50.1%, p=0.009). CONCLUSION: EGFR appears to have no prognostic value when chemoradiotherapy is used. Possibly a small subgroup of cases with stronger positivity and worse prognosis can be identified.

Gemcitabine and cisplatin in a concomitant alternating chemoradiotherapy program for locally advanced head-and-neck cancer: a pharmacology-guided schedule.

PURPOSE: Administration of gemcitabine together with cisplatin at cytotoxic doses in a chemoradiotherapy regimen is hampered by a high degree of local toxicity. Using the pharmacologic properties of the drug we designed a modified schedule aimed at reducing toxicity while preserving activity. METHODS AND MATERIALS: Patients with squamous cell carcinomas of the oral cavity, pharynx and larynx, bulky T4, and/or N2 to N3 were eligible. Gemcitabine was administered at a dose of 800 mg/m2 on Days 1 and 12 and cisplatin at a dose of 20 mg/m2 on Days 2 to 5, every 21 days for 3 courses. Radiotherapy, delivered with standard fractionation, was given on Days 8 to 12 and 15 to 19 and was repeated 3 times up to a total dose of > or = 60 Gy. RESULTS: A total of 28 patients were selected. Grade 3 to 4 stomatitis was recorded in 25 patients (89%). Thirteen patients (46%) experienced Grade 3 to 4 neutropenia. Febrile neutropenia occurred in 8 patients (29%) and in 2 was complicated by infection and death. The overall complete response rate was 79%. At a median follow up of 71 months, 11 patients had a locoregional relapse (3-year locoregional control, 64%); 6 patients had distant metastases, among whom only 2 were without locoregional recurrence. The 3-year progression-free survival is 39% and 3-year overall survival has been 43%. CONCLUSION: The schedule modification did not attenuate local toxicity. Moreover, infections and especially pneumonia, were a major problem. The high activity of gemcitabine when combined with radiotherapy would most likely be better exploited in the context of modified radiation schemes.

Weekly docetaxel and zoledronic acid every 4 weeks in hormone-refractory prostate cancer patients.

OBJECTIVES: To investigate the safety and efficacy of docetaxel and zoledronic acid in patients with hormone-refractory prostate cancer (HRPC), based on preclinical evidence of synergism between taxanes and bisphosphonates. METHODS: Twenty-five patients with advanced HRPC received weekly docetaxel 30 mg/m2: in 18 patients with symptomatic bone metastases and normal renal function, docetaxel was combined with zoledronic acid, 4 mg i.v. every 4 weeks. Premedication consisted of intravenous dexamethasone before docetaxel. No oral steroids were given. RESULTS: Overall, 12 patients (48%) had a PSA response (reduction of 50% or more compared to baseline). A PSA response was achieved in 8/18 patients (44%) receiving concomitant docetaxel and zoledronic acid, and in 7/12 patients (58%) receiving docetaxel and zoledronic acid as first-line therapy. The weekly schedule of docetaxel resulted in a mean received dose intensity of 26 mg/m2/week, or 87% of the planned dose intensity. Toxicity was mild and as expected for docetaxel. The median time to progression was 7 months, and the median overall survival was 16 months. CONCLUSIONS: Concomitant treatment with docetaxel and zoledronic acid is safe and has encouraging activity in HRPC. The combination should be evaluated in randomised clinical trials.

Paclitaxel, cisplatin, 5-fluorouracil and radiotherapy in the management of advanced squamous cell carcinoma of the head and neck: a phase II trial.

Aim of the present study was to test, activity and toxicity of a rapidly alternating chemoradiation (paclitaxel based) in 31 patients with unresectable, locally advanced or recurrent after surgery, head and neck cancer. Three-year overall survival and progression-free survival were 61.4 and 73.7%, respectively. Main side effects remain a major problem.