Targeted therapy for advanced salivary gland carcinoma based on molecular profiling: results from MyPathway, a phase IIa multiple basket study.

BACKGROUND: Systemic therapy options for salivary cancers are limited. MyPathway (NCT02091141), a phase IIa study, evaluates targeted therapies in non-indicated tumor types with actionable molecular alterations. Here, we present the efficacy and safety results for a subgroup of MyPathway patients with advanced salivary gland cancer (SGC) matched to targeted therapies based on tumor molecular characteristics. PATIENTS AND METHODS: MyPathway is an ongoing, multiple basket, open-label, non-randomized, multi-center study. Patients with advanced SGC received pertuzumab + trastuzumab (HER2 alteration), vismodegib (PTCH-1/SMO mutation), vemurafenib (BRAF V600 mutation), or atezolizumab [high tumor mutational burden (TMB)]. The primary endpoint is the objective response rate (ORR). RESULTS: As of January 15, 2018, 19 patients with SGC were enrolled and treated in MyPathway (15 with HER2 amplification and/or overexpression and one each with a HER2 mutation without amplification or overexpression, PTCH-1 mutation, BRAF mutation, and high TMB). In the 15 patients with HER2 amplification/overexpression (with or without mutations) who were treated with pertuzumab + trastuzumab, 9 had an objective response (1 complete response, 8 partial responses) for an ORR of 60% (9.2 months median response duration). The clinical benefit rate (defined by patients with objective responses or stable disease >4 months) was 67% (10/15), median progression-free survival (PFS) was 8.6 months, and median overall survival was 20.4 months. Stable disease was observed in the patient with a HER2 mutation (pertuzumab + trastuzumab, n = 1/1, PFS 11.0 months), and partial responses in patients with the PTCH-1 mutation (vismodegib, n = 1/1, PFS 14.3 months), BRAF mutation (vemurafenib, n = 1/1, PFS 18.5 months), and high TMB (atezolizumab, n = 1/1, PFS 5.5+ months). No unexpected toxicity occurred. CONCLUSIONS: Overall, 12 of 19 patients (63%) with advanced SGC, treated with chemotherapy-free regimens matched to specific molecular alterations, experienced an objective response. Data from MyPathway suggest that matched targeted therapy for SGC has promising efficacy, supporting molecular profiling in treatment determination.

Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study.

Background: In the phase 3 RADIANT-2 study, everolimus plus octreotide long-acting repeatable (LAR) showed improvement of 5.1 months in median progression-free survival versus placebo plus octreotide LAR among patients with advanced neuroendocrine tumors associated with carcinoid syndrome. The progression-free survival P-value was marginally above the prespecified threshold for statistical significance. Here, we report final overall survival (OS) and key safety update from RADIANT-2. Patients and methods: The RADIANT-2 trial compared everolimus (10 mg/day, orally; n = 216) versus placebo (n = 213), both in conjunction with octreotide LAR (30 mg, intramuscularly, every 28 days). Patients, unblinded at the time of progression or after end of double-blind core phase following primary analysis, were offered open-label everolimus with octreotide LAR (open-label phase). In the open-label phase, patients had similar safety and efficacy assessments as those in the core phase. For OS, hazard ratios (HRs) with 95% CIs using unadjusted Cox model and a Cox model adjusted for prespecified baseline covariates were calculated. Results: A total of 170 patients received open-label everolimus (143 crossed over from the placebo arm; 27 in the everolimus arm continued to receive the same treatment after unblinding). The median OS (95% CI) after 271 events was 29.2 months (23.8-35.9) for the everolimus arm and 35.2 months (30.0-44.7) for the placebo arm (HR, 1.17; 95% CI, 0.92-1.49). HR adjusted for baseline covariates was 1.08 (95% CI, 0.84-1.38). The most frequent drug-related grade 3 or 4 AEs reported during the open-label phase were diarrhea (5.3%), fatigue (4.7%), and stomatitis (4.1%). Deaths related to pulmonary or cardiac failure were observed more frequently in the everolimus arm. Conclusion: No significant difference in OS was observed for the everolimus plus octreotide LAR and placebo plus octreotide LAR arms of the RADIANT-2 study, even after adjusting for imbalances in the baseline covariates. Clinical Trial Number: NCT00412061, www.clinicaltrials.gov.

Disease characteristics, treatment patterns, and outcomes of follicular lymphoma in patients 40 years of age and younger: an analysis from the National Lymphocare Study†.

BACKGROUND: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma, with median age at diagnosis in the seventh decade. FL in young adults (YAs), defined as diagnosis at ≤40 years, is uncommon. No standard approaches exist guiding the treatment of YA FL, and little is known about their disease characteristics and outcomes. To gain further insights into YA FL, we analyzed the National LymphoCare Study (NLCS) to describe characteristics, initial treatments, and outcomes in this population versus patients aged >40 years. PATIENTS AND METHODS: Using the NLCS database, we stratified FL patients by age: 18-40 (YA), 41-60, 61-70, 71-80, and >80 years. Survival probability was estimated using Kaplan-Meier methodology. We examined associations between age and survival using hazard ratios and 95% confidence intervals (CIs) from multivariable Cox models. RESULTS: Of 2652 eligible FL patients in the NLCS, 164 (6%) were YAs. Of YA patients, 69% had advanced disease, 80% had low-grade histology, and 50% had good-risk disease according to the Follicular Lymphoma International Prognostic Index (FLIPI). Nineteen percent underwent observation, 12% received rituximab monotherapy, and 46% received chemoimmunotherapy [in 59% of these: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone)]. With a median follow-up of 8 years, overall survival (OS) at 2, 5, and 8 years was 98% (95% CI 93-99), 94% (95% CI 89-97), and 90% (95% CI 83-94), respectively. Median progression-free survival (PFS) was 7.3 years (95% CI 5.6-not reached). CONCLUSIONS: In one of the largest cohorts of YA FL patients treated in the rituximab era, disease characteristics and outcomes were similar to patients aged 41-60 years, with favorable OS and PFS in YAs. Longer-term outcomes and YA-specific survivorship concerns should be considered when defining management. These data may not support the need for more aggressive therapies in YA FL. CLINICAL TRIAL NUMBER: Roche/Genentech ML01377 (U2963n).

The 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: summary of main findings and risk factors.

We present the main findings of the 5th National Audit Project on accidental awareness during general anaesthesia. Incidences were estimated using reports of accidental awareness as the numerator, and a parallel national anaesthetic activity survey to provide denominator data. The incidence of certain/probable and possible accidental awareness cases was ~1:19 600 anaesthetics (95% CI 1:16 700-23 450). However, there was considerable variation across subtypes of techniques or subspecialties. The incidence with neuromuscular blockade was ~1:8200 (1:7030-9700), and without it was ~1:135 900 (1:78 600-299 000). The cases of accidental awareness during general anaesthesia reported to 5th National Audit Project were overwhelmingly cases of unintended awareness during neuromuscular blockade. The incidence of accidental awareness during caesarean section was ~1:670 (1:380-1300). Two thirds (82, 66%) of cases of accidental awareness experiences arose in the dynamic phases of anaesthesia, namely induction of and emergence from anaesthesia. During induction of anaesthesia, contributory factors included: use of thiopental; rapid sequence induction; obesity; difficult airway management; neuromuscular blockade; and interruptions of anaesthetic delivery during movement from anaesthetic room to theatre. During emergence from anaesthesia, residual paralysis was perceived by patients as accidental awareness, and commonly related to a failure to ensure full return of motor capacity. One third (43, 33%) of accidental awareness events arose during the maintenance phase of anaesthesia, most due to problems at induction or towards the end of anaesthesia. Factors increasing the risk of accidental awareness included: female sex; age (younger adults, but not children); obesity; anaesthetist seniority (junior trainees); previous awareness; out-of-hours operating; emergencies; type of surgery (obstetric, cardiac, thoracic); and use of neuromuscular blockade. The following factors were not risk factors for accidental awareness: ASA physical status; race; and use or omission of nitrous oxide. We recommend that an anaesthetic checklist, to be an integral part of the World Health Organization Safer Surgery checklist, is introduced as an aid to preventing accidental awareness. This paper is a shortened version describing the main findings from 5th National Audit Project - the full report can be found at http://www.nationalauditprojects.org.uk/NAP5_home#pt.

The 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: patient experiences, human factors, sedation, consent and medicolegal issues.

The 5th National Audit Project of the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland into accidental awareness during general anaesthesia yielded data related to psychological aspects from the patient, and the anaesthetist, perspectives; patients' experiences ranged from isolated auditory or tactile sensations to complete awareness. A striking finding was that 75% of experiences were for < 5 min, yet 51% of patients (95% CI 43-60%) experienced distress and 41% (95% CI 33-50%) suffered longer-term adverse effect. Distress and longer-term harm occurred across the full range of experiences but were particularly likely when the patient experienced paralysis (with or without pain). The patient's interpretation of what is happening at the time of the awareness seemed central to later impact; explanation and reassurance during suspected accidental awareness during general anaesthesia or at the time of report seemed beneficial. Quality of care before the event was judged good in 26%, poor in 39% and mixed in 31%. Three quarters of cases of accidental awareness during general anaesthesia (75%) were judged preventable. In 12% of cases of accidental awareness during general anaesthesia, care was judged good and the episode not preventable. The contributory and human factors in the genesis of the majority of cases of accidental awareness during general anaesthesia included medication, patient and education/training. The findings have implications for national guidance, institutional organisation and individual practice. The incidence of 'accidental awareness' during sedation (~1:15 000) was similar to that during general anaesthesia (~1:19 000). The project raises significant issues about information giving and consent for both sedation and anaesthesia. We propose a novel approach to describing sedation from the patient's perspective which could be used in communication and consent. Eight (6%) of the patients had resorted to legal action (12, 11%, to formal complaint) at the time of reporting. The 5th National Audit Project methodology provides a standardised template that might usefully inform the investigation of claims or serious incidents related to accidental awareness during general anaesthesia.

5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: patient experiences, human factors, sedation, consent, and medicolegal issues.

The 5th National Audit Project (NAP5) of the Royal College of Anaesthetists and the Association of Anaesthetists of Great Britain and Ireland into accidental awareness during general anaesthesia (AAGA) yielded data related to psychological aspects from the patient, and the anaesthetist, perspectives; patients' experiences ranged from isolated auditory or tactile sensations to complete awareness. A striking finding was that 75% of experiences were for <5 min, yet 51% of patients [95% confidence interval (CI) 43-60%] experienced distress and 41% (95% CI 33-50%) suffered longer term adverse effect. Distress and longer term harm occurred across the full range of experiences but were particularly likely when the patient experienced paralysis (with or without pain). The patient's interpretation of what is happening at the time of the awareness seemed central to later impact; explanation and reassurance during suspected AAGA or at the time of report seemed beneficial. Quality of care before the event was judged good in 26%, poor in 39%, and mixed in 31%. Three-quarters of cases of AAGA (75%) were judged preventable. In 12%, AAGA care was judged good and the episode not preventable. The contributory and human factors in the genesis of the majority of cases of AAGA included medication, patient, and education/training. The findings have implications for national guidance, institutional organization, and individual practice. The incidence of 'accidental awareness' during sedation (~1:15,000) was similar to that during general anaesthesia (~1:19,000). The project raises significant issues about information giving and consent for both sedation and anaesthesia. We propose a novel approach to describing sedation from the patient's perspective which could be used in communication and consent. Eight (6%) of the patients had resorted to legal action (12, 11%, to formal complaint) at the time of reporting. NAP5 methodology provides a standardized template that might usefully inform the investigation of claims or serious incidents related to AAGA.

5th National Audit Project (NAP5) on accidental awareness during general anaesthesia: summary of main findings and risk factors.

We present the main findings of the 5th National Audit Project (NAP5) on accidental awareness during general anaesthesia (AAGA). Incidences were estimated using reports of accidental awareness as the numerator, and a parallel national anaesthetic activity survey to provide denominator data. The incidence of certain/probable and possible accidental awareness cases was ~1:19,600 anaesthetics (95% confidence interval 1:16,700-23,450). However, there was considerable variation across subtypes of techniques or subspecialities. The incidence with neuromuscular block (NMB) was ~1:8200 (1:7030-9700), and without, it was ~1:135,900 (1:78,600-299,000). The cases of AAGA reported to NAP5 were overwhelmingly cases of unintended awareness during NMB. The incidence of accidental awareness during Caesarean section was ~1:670 (1:380-1300). Two-thirds (82, 66%) of cases of accidental awareness experiences arose in the dynamic phases of anaesthesia, namely induction of and emergence from anaesthesia. During induction of anaesthesia, contributory factors included: use of thiopental, rapid sequence induction, obesity, difficult airway management, NMB, and interruptions of anaesthetic delivery during movement from anaesthetic room to theatre. During emergence from anaesthesia, residual paralysis was perceived by patients as accidental awareness, and commonly related to a failure to ensure full return of motor capacity. One-third (43, 33%) of accidental awareness events arose during the maintenance phase of anaesthesia, mostly due to problems at induction or towards the end of anaesthesia. Factors increasing the risk of accidental awareness included: female sex, age (younger adults, but not children), obesity, anaesthetist seniority (junior trainees), previous awareness, out-of-hours operating, emergencies, type of surgery (obstetric, cardiac, thoracic), and use of NMB. The following factors were not risk factors for accidental awareness: ASA physical status, race, and use or omission of nitrous oxide. We recommend that an anaesthetic checklist, to be an integral part of the World Health Organization Safer Surgery checklist, is introduced as an aid to preventing accidental awareness. This paper is a shortened version describing the main findings from NAP5--the full report can be found at http://www.nationalauditprojects.org.uk/NAP5_home.

Improved time to treatment failure with an intermittent oxaliplatin strategy: results of CONcePT.

BACKGROUND: Oxaliplatin is an integral component of colorectal cancer treatment, but its use is limited by neurotoxicity. The Combined Oxaliplatin Neurotoxicity Prevention Trial (CONcePT) tested intermittent oxaliplatin (IO) administration and the use of concurrent calcium and magnesium salts (Ca/Mg), two modifications intended to reduce neurotoxicity and extend the duration of treatment. PATIENTS AND METHODS: In this trial involving double randomization, 140 patients were randomized to receive modified FOLFOX7 plus bevacizumab with IO (eight-cycle blocks of oxaliplatin treatment) versus continuous oxaliplatin (CO); and Ca/Mg versus placebo (pre- and postoxaliplatin infusion). The primary end point was time-to-treatment failure (TTF). RESULTS: One hundred thirty-nine patients were entered and treated up to the point of early study termination due to concerns by the data-monitoring committee (DMC) that Ca/Mg adversely affected tumor response. Tumor response was not a study end point. Given DMC concerns, an additional independent, blinded radiology review of all images showed no adverse effect of treatment schedule or Ca/Mg on response by Response Evaluation Criteria In Solid Tumors. The IO schedule was superior to CO [hazard ratio (HR) = 0.581, P = 0.0026] for both TTF and time-to-tumor progression (TTP) (HR = 0.533, P = 0.047). CONCLUSIONS: An IO dosing schedule had a significant benefit on both TTF and TTP versus CO dosing in this trial despite the very attenuated sample. There was no effect of Ca/Mg on response.

Carcinoma of unknown primary with gastrointestinal profile: immunohistochemistry and survival data for this favorable subset.

BACKGROUND: Carcinoma of unknown primary with a "gastrointestinal profile" is an emerging, favorable entity. Distinguishing this entity is of increasing significance given the progress in the treatment of colorectal cancer. PATIENTS AND METHODS: 74 carcinoma of unknown primary (CUP) patients with CDX2+ tumors were chosen from the databases at M.D. Anderson and Sarah Cannon Cancer Centers between 2004 and 2010. Data on clinical and pathological characteristics including therapy and survival were recorded. RESULTS: 20 patients had ascites on presentation; the predominant sites of metastases included liver (30 %), carcinomatosis (50 %), and nodes (51 %). Based on immunohistochemistry, 2 cohorts were created: Cohort 1-"consistent with lower GI profile" included 34 patients [CDX-2+, CK20+, CK7-] and Cohort 2-"probable lower GI profile" included 40 patients [CDX2+, irrespective of CK7/CK20 status]. Excluding 6 outliers, Cohorts 1 and 2 had 32 and 36 patients, respectively; their median survivals were 37 and 21 months, respectively. On multivariate Cox regression analysis, only liver metastases were found to negatively influence survival. CONCLUSIONS: Our retrospective study provides encouraging indications that CUP patients with gastrointestinal profiles benefit from site-specific therapy. We recommend all CUP patients, especially those with abdominal nodes, isolated carcinomatosis or liver metastases, to undergo optimal immunohistochemistry (IHC) to check for a gastrointestinal profile of CUP.

Psychosocial characteristics of adults who experience difficulties with retching.

OBJECTIVES: The current study aimed to reach a greater understanding of psychosocial variables in patients who gag, and is a recognised gap within current literature. Obtaining a profile of patients who gag could provide valuable information in relation to future treatment planning and management of this type of difficulty. METHODS: All new patients aged > or =18 years, identified as having a difficulty with retching, and who attended the Anxiety Management Clinic, Department of Restorative Dentistry, Birmingham Dental Hospital, were invited to complete a brief questionnaire with questions related to general demographic data; difficulties with retching; and an oral health status measurement. This study has reported on 48 patients who attended the dental anxiety management clinic at Birmingham Dental Hospital and who presented with retching difficulties. One patient did not wish to take part in the study, leaving a final sample size of 47. The sample comprised 57% male (n=27) and 43% female (n=20) patients. RESULTS: Retching was more commonly seen in the 40-49-year age group. Onset was frequently related to an earlier dental experience and over half the sample studied had experienced previous psychological difficulties. A fear of choking or suffocation was frequently expressed, supporting a cognitive model in terms of assessment and treatment. CONCLUSION: A number of themes were identified which would be worthy of further exploration. For example, the impact of previous or existing physical health problems such as respiratory complaints, family history of retching, and prevalence of other psychological difficulties. Through participation in this study, patients were able to reach a greater awareness of this commonly encountered difficulty within dentistry.

Evaluation of dentists' perceived needs regarding treatment of the anxious patient.

BACKGROUND: With regard to the management of dental anxiety in general dental practice, it has been considered that general dental practitioners (GDPs) are well placed to treat adults with mild forms of dental anxiety. However, little is known about the specific anxiety management techniques being used by GDPs in the UK. Aim To determine the views and experiences of dental practitioners in their current use of anxiety management techniques, their undergraduate and post-graduation training in these techniques and future training needs. METHODS: A postal questionnaire was sent to a sample of GDPs working in the Midlands region (n = 750) in the UK. Dentists were randomly selected using lists provided by the primary care trusts for each locality. RESULTS: The response rate was 73% (n = 550). Of these, 90 were not included in the final analysis due to exclusion criteria set prior to questionnaire release. This left 460 questionnaires for analysis. Eighty-five percent of respondents agreed that dentists had a responsibility to help dentally anxious patients (n = 391). Dentists were asked their reasons for not using anxiety management techniques in practice. Psychological techniques, sedation (oral, inhalation, or intravenous) and hypnosis were reported as not having been used due to the paucity of time available in practice, a shortage of confidence in using these techniques and the lack of fees available under the NHS regulations. Also, 91% reported feeling stressed when treating anxious patients. When asked about the quality of teaching they had received (undergraduate and postgraduate), 65% considered that the teaching was less than adequate in the use of psychological methods, whereas 44% indicated that they would be interested in further training in psychological methods if financial support was available. CONCLUSION: The need for further training in managing the dentally anxious patient is supported by dentists' lack of confidence and inadequate training in treating such patients, as determined from the results of a postal questionnaire to UK GDPs.

Relaxation and complementary therapies: an alternative approach to managing dental anxiety in clinical practice.

Dental anxiety is a widespread problem and has a significant impact on the provision of dental care for the general population. Anxiety leads to avoidance of dental treatment and increased stress for dental practitioners. Traditionally, dental anxiety has been managed using pharmacological techniques. This article reviews alternative treatment approaches, including psychological and complementary therapies which can be used in managing dental anxiety and facilitating dental treatment. Many of these approaches are currently being used within the dental profession. Others are gaining a wider acceptance as to their usage. Where available, the evidence of their efficacy will be reviewed.

Panel discussion on B cells and rituximab: mechanistic aspects, efficacy and safety in rheumatoid arthritis and non-Hodgkin's lymphoma.

The clinical potential of rituximab (MabThera/Rituxan), a selective B-cell-depleting agent, in the treatment of patients with rheumatoid arthritis (RA) is rapidly becoming apparent. The data presented at an official satellite symposium of the European League Against Rheumatism (EULAR) Congress (2003, Lisbon, Portugal), reinforce the rationale for the use of this novel agent in RA and have provided an early indication of its clinical efficacy, safety and tolerability. The symposium presentations were followed by a panel discussion and a question and answer session in which the participants were able to shed further light on specific mechanistic issues relating to effects on B-cell populations based on available data and their own clinical experience of rituximab. Additionally, the implications of current results for longer-term clinical efficacy and safety were discussed. It is becoming clear that rituximab (alone or in combination with disease-modifying anti-rheumatic drugs) is highly efficacious in RA. Extensive data from patients with non-Hodgkin's lymphoma show that early concerns over increased infection rates due to prolonged suppression of B cells have not been realized. The effects of rituximab on long-term RA outcomes, such as joint erosion and duration of response (particularly in patients receiving combination therapy), are eagerly anticipated.

A review of self-management interventions for panic disorders, phobias and obsessive-compulsive disorders.

OBJECTIVE: To review current evidence for the clinical and cost-effectiveness of self-management interventions for panic disorder, phobias and obsessive-compulsive disorder (OCD). METHOD: Papers were identified through computerized searches of databases for the years between 1995 and 2003, manual searches and personal contacts. Only randomized-controlled trials were reviewed. RESULTS: Ten studies were identified (one OCD, five panic disorder, four phobias). Effective self-management interventions included cognitive-behavioural therapy (CBT) and exposure to the trigger stimuli for phobias and panic disorders. All involved homework. There was evidence of effectiveness in terms of improved symptoms and psychological wellbeing when compared with standard care, waiting list or relaxation. Brief interventions and computer-based interventions were effective for most participants. In terms of quality, studies were mainly based on small samples, lacked long-term follow-up, and failed to address cost-effectiveness. CONCLUSION: Despite the limitations of reviewed studies, there appears to be sufficient evidence to warrant greater exploration of self-management in these disorders.

Diagnostic and therapeutic management of cancer of an unknown primary.

Metastatic Cancer of Unknown Primary Site (CUP) accounts for approximately 3% of all malignant neoplasms and is therefore one of the 10 most frequent cancer diagnoses in man. Patients with CUP present with metastatic disease for which the site of origin cannot be identified at the time of diagnosis. It is now accepted that CUP represents a heterogeneous group of malignancies that share a unique clinical behaviour and, presumably, unique biology. The following clinicopathological entities have been recognised: (i) metastatic CUP primarily to the liver or to multiple sites, (ii) metastatic CUP to lymph nodes including the sub-sets involving primarily the mediastinal-retroperitoneal, the axillary, the cervical or the inguinal nodes, (iii) metastatic CUP of peritoneal cavity including the peritoneal papillary serous carcinomatosis in females and the peritoneal non-papillary carcinomatosis in males or females, (iv) metastatic CUP to the lungs with parenchymal metastases or isolated malignant pleural effusion, (v) metastatic CUP to the bones, (vi) metastatic CUP to the brain, (vii) metastatic neuroendocrine carcinomas and (viii) metastatic melanoma of an unknown primary. Extensive work-up with specific pathology investigations (immunohistochemistry, electron microscopy, molecular diagnosis) and modern imaging technology (computed tomography (CT), mammography, Positron Emission Tomography (PET) scan) have resulted in some improvements in diagnosis; however, the primary site remains unknown in most patients, even on autopsy. The most frequently detected primaries are carcinomas hidden in the lung or pancreas. Several favourable sub-sets of CUP have been identified, which are responsive to systemic chemotherapy and/or locoregional treatment. Identification and treatment of these patients is of paramount importance. The considered responsive sub-sets to platinum-based chemotherapy are the poorly differentiated carcinomas involving the mediastinal-retroperitoneal nodes, the peritoneal papillary serous adenocarcinomatosis in females and the poorly differentiated neuroendocrine carcinomas. Other tumours successfully managed by locoregional treatment with surgery and/or irradiation are the metastatic adenocarcinoma of isolated axillary nodes, metastatic squamous cell carcinoma of cervical nodes, or any other single metastatic site. Empirical chemotherapy benefits some of the patients who do not fit into any favourable sub-set, and should be considered in patients with a good performance status.

Weekly docetaxel with either gemcitabine or vinorelbine as second-line treatment in patients with advanced nonsmall cell lung carcinoma: Phase II trials of the Minnie Pearl Cancer Research Network.

BACKGROUND: The current study was conducted to evaluate the feasibility, toxicity, and efficacy of weekly docetaxel when paired with either gemcitabine or vinorelbine as the second-line treatment of patients with advanced nonsmall cell lung carcinoma. METHODS: Patients with progressive nonsmall cell lung carcinoma after one previous chemotherapeutic regimen, an Eastern Cooperative Oncology Group performance status of 0-2, and measurable lesions were eligible for treatment in these Phase II trials. Patients who had not received gemcitabine previously were treated with docetaxel, 30 mg/m(2), and gemcitabine, 800 mg/m(2), both of which were administered intravenously (i.v.) on Days 1, 8, and 15 of a 28-day cycle. If the patients had received gemcitabine as part of first-line therapy, they were treated with docetaxel, 30 mg/m(2), and vinorelbine, 20 mg/m(2) i.v., on Days 1, 8, and 15 of a 28-day cycle. Patients were reevaluated after two courses of treatment, and responding patients continued treatment for six courses or until disease progression. RESULTS: Forty patients were treated with a combination of docetaxel and gemcitabine, and 23 patients received docetaxel and vinorelbine. The docetaxel/gemcitabine combination was reasonably well tolerated, with moderate myelosuppression and a few nonhematologic toxicities reported. The objective response rate was 10%, with a 1-year survival rate of 20%. The docetaxel/vinorelbine combination was found to be poorly tolerated, with Grade 3/4 leukopenia reported in 71% of patients and neutropenic fever reported in 70% of patients despite frequent dose reductions and omission of the Day 15 doses. Enrollment onto this regimen was stopped prematurely due to toxicity, and after no major responses were observed in the first 20 evaluable patients. CONCLUSIONS: The combination of weekly docetaxel/gemcitabine appears to be feasible and relatively well tolerated as second-line treatment in patients with advanced nonsmall cell lung carcinoma, whereas a weekly combination of docetaxel and vinorelbine did not appear to be tolerable at the doses and schedule used in the current study. Neither regimen showed a level of activity that suggested any advantage compared with the results obtained with single-agent docetaxel in this setting.

Paclitaxel and carboplatin adjuvant therapy alone or with radiotherapy for resected nonsmall cell lung carcinoma: a feasibility study of the Minnie Pearl Cancer Research Network.

BACKGROUND: The objective of this study was to determine the feasibility and toxicity of paclitaxel and carboplatin given in the adjuvant setting alone for patients with resected Stage IB disease and combined with radiotherapy for patients with resected Stages II and IIIA disease and selected patients with Stage IIIB and IV disease (Revised International System for Staging of Lung Cancer). METHODS: One hundred two patients with resected nonsmall cell lung carcinoma were treated in the postoperative period with 3 courses of paclitaxel 200 mg/m(2) intravenously (i.v.) over 1 hour and carboplatin area under the curve of 6 i.v. every 3 weeks for 3 courses. Patients with Stage IB received no further therapy, and those with higher stages also subsequently received radiotherapy plus concurrent weekly paclitaxel and carboplatin over 6 weeks. The median age was 61 years, with 56 men and 46 women, and the predominant histologic type was adenocarcinoma. Twenty pneumonectomies, 80 lobectomies, and 2 other procedures were performed. Ninety percent of the patients (92 of 102) received all 3 courses of adjuvant paclitaxel and carboplatin (84% received full doses). Seventy-three percent received full doses of radiotherapy and concurrent weekly chemotherapy (49 of 67 patients), and 14 others received greater than 75% of the radiotherapy and concurrent chemotherapy. RESULTS: Toxicity of the chemotherapy was mild with only three hospitalizations for neutropenia and fever and no treatment-related deaths. Severe hypersensitivity occurred in six patients (6%). Concurrent radiation therapy and weekly chemotherapy also was well tolerated with the exception of Grade 3-4 esophagitis observed in 27% (17 of 67 patients). Follow-up was short with a median of 10 months, and 65% of all patients remained progression free. CONCLUSIONS: Three courses of paclitaxel and carboplatin is tolerable, feasible, and can be delivered in most patients in the adjuvant setting. Subsequently, in higher stage patients, concurrent postoperative radiation therapy and weekly paclitaxel and carboplatin is well tolerated and delivered in most patients. Definitive prospective randomized Phase III adjuvant trials are warranted.

Volunteers' experiences of becoming arthritis self-management lay leaders: "It's almost as if I've stopped aging and started to get younger!".

OBJECTIVE: To determine whether undergoing training to become a lay leader and conducting an arthritis self-management course is associated with improvements in physical and psychological health status, arthritis self-efficacy, use of self-management techniques, and visits to the general practitioner. In addition, we aimed to describe the experiences of training and course delivery from the older volunteers' perspective. METHODS: 21 participants completed all assessments and had a median age of 58, median disease duration of 10 years, and either osteoarthritis (n = 13) or rheumatoid arthritis (n = 8). The study was a pretest-posttest design with qualitative data collected at 3 points in time: before training, 6 weeks after training, and 6 months after training. Quantitative data were collected through self-administered postal questionnaires at baseline and 6-month followup. RESULT: Six months after training, participants reported small, significant increases in arthritis self-efficacy for pain (P = 0.002), cognitive symptom management (P = 0.004), and communication with their physician (P = 0.024) and a small, significant decrease in depressed mood (P = 0.04). Qualitative data supported these findings, with participants reporting more confidence, happiness, and a changed outlook on life in general. Volunteerism was associated with altruistic behavior and with filling the vocational void caused by retirement. CONCLUSION: Findings support the value of volunteerism and training to become lay leaders in arthritis self-management programs. Volunteers reported positive changes both in themselves and in course participants. They enjoyed helping similar others and being involved in a worthwhile activity, and they valued their newly acquired status as lay leaders. Many had begun to apply their newfound knowledge about self-management to their own situation, reporting less pain and more willingness "to get on with life."