Stiff person syndrome (SPS) is a rare clinical disorder presenting with progressive muscle stiffness and painful spasms. Its ill-defined mechanism and variable presentation make diagnosis a challenge, though it is associated with a range of specific auto-antibodies. One particular antibody, anti-amphiphysin, is found in the presence of breast or lung malignancy and leads to a disorder termed paraneoplastic SPS (PSPS). Our patient, an 83-year-old woman, presented with bilateral leg weakness, spasms, and left clubfoot over a period of three months. She also reported a lump in her left breast for which she had not sought treatment over the past 10 years. Her ankle radiograph was negative for fractures and dislocations, while an MRI of the left leg was negative for plexopathies. Electromyography was suggestive of an SPS disorder and a positive anti-amphiphysin test indicated a diagnosis of PSPS. Her symptoms were managed with baclofen, diazepam, and five cycles of therapeutic plasma exchange (TPEX) over 10 days. Breast imaging revealed a 4.5-cm left breast lesion, later biopsy-confirmed as invasive ductal carcinoma (ER+, PR+, HER2−). The patient declined definitive surgical management, opting instead for once-daily anastrozole 1 mg as hormonal therapy. This regimen was not sufficient to lead to symptomatic improvement over a period of more than 30 days, and the patient expired less than 45 days after discharge. To our knowledge, this is the first case of PSPS to be treated in this manner. Our report illustrates that conservative management with anastrozole monotherapy was not sufficient to lead to symptomatic improvement in this form of paraneoplastic syndrome, suggesting the need for more aggressive pharmacological or definitive surgical intervention in order to produce symptom improvement and/or resolution.

Background Panitumumab is a fully human monoclonal antibody that targets EGFR. We aimed to compare chemoradiotherapy plus panitumumab with chemoradiotherapy alone in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck.Methods In this international, open-label, randomised, controlled, phase 2 trial, we recruited patients with locally advanced squamous-cell carcinoma of the head and neck from 41 sites in nine countries worldwide. Patients aged 18 years and older with stage III, IVa, or IVb, previously untreated, measurable (>= 10 mm for at least one dimension), locally advanced squamous-cell carcinoma of the head and neck (non-nasopharygeal) and an Eastern Cooperative Oncology Group performance status of 0-1 were randomly assigned (2:3) by an independent vendor to open-label chemoradiotherapy (three cycles of cisplatin 100 mg/m(2)) or panitumumab plus chemoradiotherapy (three cycles of intravenous panitumumab 9.0 mg/kg every 3 weeks plus cisplatin 75 mg/m(2)) using stratified randomisation with a block size of five. All patients received 70 Gy to gross tumour and 50 Gy to areas at risk for subclinical disease with standard fractionation. The primary endpoint was local-regional control at 2 years, analysed in all randomised patients who received at least one dose of their assigned protocol-specific treatment (chemotherapy, radiation, or panitumumab). The trial is closed and this is the final analysis. This trial is registered with ClinicalTrials.gov, number NCT00500760.Findings Between Oct 26, 2007, and March 26, 2009, 153 patients were enrolled and 150 received treatment (63 in the chemoradiotherapy group and 87 in the panitumumab plus chemoradiotherapy group). Local-regional control at 2 years was 68% (95% CI 54-78) in the chemoradiotherapy group and 61% (50-71) in the panitumumab plus chemoradiotherapy group. The most frequent grade 3-4 adverse events were dysphagia (17 [27%] of 63 patients in the chemoradiotherapy group vs 35 [40%] of 87 in the panitumumab plus chemoradiotherapy group), mucosal inflammation (15 [24%] vs 48 [55%]), and radiation skin injury (eight [13%] vs 27 [31%]). Serious adverse events were reported in 20 (32%) of 63 patients in the chemoradiotherapy group and in 37 (43%) of 87 patients in the panitumumab plus chemo radio therapy group.Interpretation In patients with locally advanced squamous-cell carcinoma of the head and neck, the addition of panitumumab to standard fractionation radiotherapy and cisplatin did not confer any benefit, and the role of EGFR inhibition in these patients needs to be reassessed.

Collaborations between physicians, particularly those in academic medicine, and industries that develop pharmaceutical products, medical devices, and diagnostic tests have led to substantial advances in patient care. At the same time, there is a strong awareness that these relationships, however beneficial they may be, should conform to established principles of ethical professional practice. Through a writing committee drawn from diverse disciplines across several institutions, the Association of Clinical Researchers and Educators (ACRE) has written a code of conduct to provide guidance to physicians in observing these principles. Our recommendations are not intended to be prescriptive or inflexible, but rather to be of assistance to physicians in making their own personal decisions on whether, or how, to be involved in research, education, or other collaborations with industry.

Rituximab is a chimeric monoclonal antibody targeting the pan-B-cell antigen CD20 and was the first monoclonal antibody approved for clinical use in the treatment of cancer. Since its first approval by the FDA in 1997, investigators have continued to explore a variety of clinical conditions in which rituximab has proven effective with minimal toxicity. Rituximab, as monotherapy or in combination with chemotherapy, has been studied extensively in untreated and relapsed/refractory settings as both induction and maintenance therapy for the treatment of CD20-positive lymphomas and chronic lymphocytic leukemia, in addition to non-malignant hematologic disorders including autoimmune hemolytic anemia and immune thrombocytopenic purpura. Here we discuss the clinical development of rituximab with a review of the efficacy data from clinical trials and its current status in the practice of hematology and oncology.

5502 Background: Pmab is a fully human monoclonal antibody against the epidermal growth factor receptor. We evaluated the safety and efficacy in pts receiving CRT alone or CRT plus pmab (PCRT) as 1st‑line treatment of LASCCHN (sponsored and funded by Amgen Inc.). Methods: Pts with stage III, IVA, or IVB previously untreated LASCCHN of all sites excluding the nasopharynx were randomized 2:3 to open-label CRT or PCRT. CRT included cisplatin 100 mg/m2 for 3 cycles during standard fractionation radiotherapy (RT). PCRT included pmab 9.0 mg/kg + cisplatin 75 mg/m2, both administered with RT as in the CRT arm. The primary endpoint was local regional control (LRC) rate at 2 years; key secondary endpoints included PFS, OS, and safety. Preplanned HPV subset analysis, as determined by p16 immunohistochemistry, was performed on available samples. Results: Of 150 treated pts (87 pts PCRT, 63 pts CRT), 87% were men; median (range) age was 57 (39-77) years; ECOG PS 0: 68%. Of 99 pts with tumor evaluable for HPV, 42% were HPV+. Overall, the 2-year LRC rate (95% CI) was 61% (50%-71%) for PCRT and 68% (54%-78%) for CRT. PFS events occurred in 40% of the PCRT and 35% of CRT arm (HR [95% CI] 1.15 [0.68-1.96]; p=0.61). Death occurred in 36% of the PCRT arm vs 24% of the CRT arm (HR [95% Cl] for OS 1.63 [0.88-3.02]; p=0.12). Disease progression was the cause of death in 22% of PCRT pts and 10% of CRT pts. There were no differences in outcome by tumor HPV status. No difference in fatal adverse events (AEs) was seen between arms. Grade 3+ AEs occurred in 85% vs 68% of pts (PCRT vs CRT). Differences in grade 3+ toxicity between treatment arms (PCRT, CRT) were most pronounced for mucosal inflammation (55%, 24%), radiation skin injury (28%, 13%), dysphagia (40%, 27%), and rash (11%, 0%). RT delays of >10 days occurred in 16% of the PCRT arm and 3% of the CRT arm. Median cisplatin cumulative dose received was 223.1 mg/m2 in the PCRT arm and 296.9 mg/m2 in the CRT arm, reflective of differences in planned dose. Conclusions: The addition of pmab to CRT did not show an increase in efficacy and was associated with increased toxicity. Further results of HPV biomarker analysis will be presented.

e14686 Background: Hepatocellular carcinoma (HCC) is the 3rd leading cause of cancer death globally with most deaths occurring within 1 year of diagnosis. Arsenic trioxide (ATO) has proven activity in the treatment of both solid and hematologic tumors. ATO cytotoxicity and apoptosis induction has been demonstrated in vitro with numerous human cancer cell lines including HCC. Methods: Patients with advanced measurable HCC, no more than one prior systemic treatment or no treatment, ECOG PS 0-2 and Child-Pugh class A received ATO 0.35 mg/kg on days 1, 8, 15, and 22 of each 28-day cycle. The primary endpoints were the feasibility of administering this regimen and the qualitative and quantitative toxicities of treatment. Secondary endpoints were response to treatment, duration of progression-free survival, patterns of failure, and survival. Results: 9 patients were enrolled from 10/13/04 to 9/5/07. Median age of patients was 57 years (range 50-62 years) and included 8 males and 1 female. No patients had previous systemic therapy. 3 patients did not complete the first cycle and were not evaluable for response. 6 patients had progressive disease on therapy. 1 patient received 8 cycles of therapy, achieved a partial response lasting 8 months and is still alive. Most common adverse effects (AEs) were fatigue and QTC prolongation and all AEs were less than grade 3. No patients had APL differentiation syndrome. Conclusions: Although ATO demonstrated 1 partial response in this trial, ATO appears to be less active than sorafenib which is FDA approved for treatment of advanced HCC. Given the complexity of therapy and potential cardiotoxicity, further development of ATO in this setting appears unwarranted. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cepahlon, GlaxoSmithKline, Lilly Cepahlon

Background Since its advent, endoscopic ultrasonography (EUS) has emerged as an invaluable tool in the diagnosis and management of gastrointestinal and adjacent cancers. Yet, it remains unclear how non-gastroenterologists who manage these malignancies use EUS in their practices. Methods A link to a self-administered questionnaire, hosted on our university website, was emailed to 650 practicing medical, radiation, and surgical oncologists in the United States. Results Data were analyzed from 100 responses. When available, the overall utilization of EUS for staging nonsmall cell lung cancer (NSCLC) was significantly low (19.0%), although available. When EUS was unavailable, majority of the patients with pancreatobiliary cancer (79%; P<0.01) were not referred for staging, unlike those with esophageal (57.9%) and rectal cancer (73.7%) were. EUS availability did not impact its use in staging gastric cancer. Majority of the respondents thought EUS made an impact in managing patients with rectal (89.5%), esophageal (84.5%), and pancreatobiliary cancers (58.5%) but not gastric (54.7%) or NSCLC (61.5%). In staging NSCLC, endoscopic ultrasound-guided fine-needle aspirate (35.7%) and mediastinoscopy (34.7%) were noted as the most accurate for tissue sampling of lymph nodes in levels 5, 7, and 8. EUS was deemed better than computerized tomography or magnetic resonance imaging by 42% in detecting small pancreatic tumors. Majority have not referred patients for EUS-guided celiac plexus neurolysis for palliation of pain in unresectable pancreatic cancer. Conclusions These data highlight the utilization of EUS that did not necessarily follow established guidelines. Further research is essential to evaluate obstacles to utilization of endoscopic ultrasound-guided fine-needle aspirate.

TOTHE EDITOR: Thereare several pharmaceutical companies that manufacturegeneric6-mercaptopurine tablets.The incidentdescribedhere involves the products producedby the Mylan and Par pharmaceutical companies. Case Report. Duringa routine clinicvisit,theparents of a 7-year-old boy diagnosedwithacute lymphocytic leukemiain November2004 reported to the oncologist that the patient had developed a red maculopapularrash after their localpharmacydispensed a different brandof 6-mercaptopurine tabletsthan the one he had previously taken.The patienthad beentakingoralmethotrexate 17.5 mg onceweekly and6-mercaptopurine75 mg daily (lIJz tablets) for 2 years.The rash, which appeared2 days after startingthe differentbrandof mercaptopurine, was locatedon his chest.back,and arms and was slightlypruritic.It continuedforapproximately 3 weekswithout improving or worsening. The parents had considered otherpossible causes.suchas a changein diet, other medications, or laundrydetergent; however, mercaptopurine appeared to be theonly likelycause.When the different brandof tablets (MylanLaboratories) was dispensed, the parentsverifiedwith thepharmacistthat the tabletswere indeedmercaptopurine. After3 weeks,they requested that the pharmacist order the original brand(Par Pharmaceutical) for their son. The rash began to resolve 2 days after discontinuing the Mylanbrandandresuming the Parbrand.It wascompletely goneafter 1week.Hehascontinued his treatment withtheParbrandwithout recurrence of the rash. Discussion.The oncologistaskedthe clinicalpharmacyspecialistin the hematology clinic to investigate this incident.She obtaineda list of excipientsfrom each manufacturer. The Mylanbrand is a white round tablet that containslactosemonohydrate, magnesium stearate(bovine), pregelatinized starch/cornstarch, and starch(driedcorn).' The Par brand is a light yel1ow, diamond-shaped tablet that containsmicrocrystalline cellulose NF,lactosemonohydrate NF,stearic acidNF,andcolloidal siliconedioxideNF.lAfter the clinicpharmacist notedthat the main difference between the tablet formulations was the use of cornstarch, she asked the patient's mother if he was al1ergic to cornstarch.The mother statedthat he had been testedby an al1ergist and it was determined that he was indeed allergic to cornstarch. This information was not documentedin the medicalrecord.The motherstatedthat therehad been no previous reactions to cornstarch. This case demonstrates that inactiveingredients, as wel1 as the medicationsthemselves, are possible causesforallergic reactions. The Naranjo probability scale revealedthat the rash was a probableadversereaction to the cornstarchin the Mylan brand tablet.' If this patienthad not previously tolerateda different brandof 6-mercaptopurine, it may have beenassumed thathe was allergic to the activeingredient, a crucial drug in the treatmentof his leukemia.In that case, the oncologistwould not have discontinuedmercaptopurine,but the child would possibly have had to endurea constantrash for 2 yearsunlessa brandchangeoccurred and the rash resolved. When an al1ergic reaction occurs, pharmacists shouldconsider bothactiveandinactive ingredients as possible causes.

BACKGROUND. The authors assessed patterns of perioperative chemotherapy use in elderly patients with resected stage I, II, or IIIA nonsmall cell lung cancer (NSCLC) from 1992 to 2002.METHODS. By using data from the Surveillance, Epidemiology, and End Results Program, 11,807 patients were identified who had resected stage I, II, or IIIA NSCLC between 1992 and 2002 and survived >= 120 days beyond diagnosis. The rate of perioperative chemotherapy use was measured by calendar year, and the association between clinical/demographic characteristics and the receipt of chemotherapy was examined by using logistic regression.RESULTS. in total, 957 patients with stage I, II, or IIIA NSCLC (8.1% of the study population) received perioperative chemotherapy. The proportion of patients receiving chemotherapy for stage I NSCLC changed little during the study period. Of 3230 patients with stage II and IIIA NSCLC, 609 patients (18.9%) received chemotherapy, 423 patients (13%) received chemotherapy combined with radiation. 452 patients (15.6%) received adjuvant chemotherapy, and 66 patients (2.3%) received neoadjuvant chemotherapy. The use of chemotherapy increased significantly among patients who were diagnosed after 1994 relative to patients who were diagnosed in 1992 after controlling for sociodemographic and treatment characteristics (P < .001). There was significantly increased use of new-generation chemotherapy agents, such as carboplatin and taxanes (P < .001). The proportion of patients receiving combined-modality therapy also increased significant (P < .001). Younger age, being married, having advanced-stage tumor or adenocarcinoma, having a later diagnosis year, receiving radiation, and seeing an oncologist were predictors for the receipt of chemotherapy (P < .001).CONCLUSIONS. A substantial proportion of Medicare beneficiaries with NSCLC received perioperative chemotherapy. Specifically designed prospective trials that focus on older patients are needed.

Purpose: Endoscopic Ultrasonography (EUS) is well established for the evaluation of mediastinal lymph nodes as a diagnostic or staging modality in patients with lung cancer. Various sonographic criteria have been described for diagnosis of malignant spread but EUS guided fine needle aspiration (FNA) has shown to be superior to lymph node echofeatures. The objective of this study is to determine if computer-assisted analysis of mediastinal lymph nodes can be reliable for predicting malignant spread when EUS-FNA is not feasible due to location or other technical difficulties. Methods: A retrospective IRB approved chart review of EUS was done for the evaluation of mediastinal LNs with the indication of suspected or diagnosed lung cancer from May 2002 to June 2005. The diagnosis was accepted as malignant mediastinal lymph nodes when FNA cytology was positive. When cytology was non-malignant, the results were compared with the final surgical pathological diagnosis of excised lymph nodes. An experienced endosonographer (MSB) selected lymph node images for analysis. JAVA based software (Image J, available at http://rsb.info.nih.gov/ij) was used to analyze the echogenicity of lymph node images obtained by EUS. The mean density of lymph nodes was used as a marker for echogenicity. Results: Out of a total of 58 EUS procedures, 26 patients were included per criteria. 11/26 patients had benign lymph nodes and 15/26 patients had malignant LNs. The mean density was obtained by the lymph node border-tracing method using Image J. No significant difference was found between the mean densities of malignant LNs when compared with benign LNs (p= 0.32). Conclusions: Image J appears not to be a useful study for differentiation of malignant from benign lymph nodes on EUS imaging. We need to use more sophisticated image analysis software for reliable computer aided differentiation of nodal spread of malignancy.

Previous data suggested interaction of cisplatin with interferon (IFN) in non-small cell lung cancer and a possible effect of IFN in maintaining remission in small cell lung cancer (SCLC). This study was designed to further examine the effect of IFN in the treatment of extensive disease (ED) SCLC. Forty previously untreated patients with performance status (PS) of 0-2 (Zubrod scale) were treated with etoposide (100 mg/m2 for 3 days), cisplatin (25 mg/m2 for 3 days) (EP), and recombinant IFN-alpha2a (rIFN-alpha2a) (5 x 10(6) U/m2 for 3 days) for six cycles (induction), followed by rIFN-alpha2a (5 x 10(6) U/m2) thrice weekly and megestrol acetate (40 mg q.i.d.) as maintenance therapy for 6 months or until progressive disease or intolerable toxicity was documented. Patients were 25 men (62%) and 15 women (38%), median age 58 (28-76), median Zubrod performance status 1 (0-2). Major sites of metastasis include liver (55%), bone (42%), bone marrow (25%), and adrenal gland (18%). Of 40 eligible patients accrued to this trial, 35 were evaluable for response, and 37 were evaluable for toxicity. There were 3 complete and 28 partial responses, for an overall response rate of 89%. With 39 of 40 patients followed until death, median survival (Kaplan-Meier) is estimated at 46 weeks (95% CI range 35-55). Twenty patients completed six cycles of induction, and 16 received maintenance therapy, median 2 cycles (range 1-3). Major toxicity during induction included grade 4 granulocytopenia in 24%, grade 2-3 nausea or vomiting or both in 41%, grade 2 fatigue in 24%, grade 2 anorexia in 22%, and grade 2-3 renal insufficiency in 9% of 175 total courses of chemotherapy administered. Toxicity during the maintenance phase was notable for grade 2-3 fatigue in 43%, grade 2-3 anorexia in 24%, grade 2-3 weight loss in 10%, and grade 3-4 anemia in 17% of 30 courses. There were no treatment-related deaths. The addition of rIFN-alpha2a to EP in induction chemotherapy of ED SCLC, followed by rIFN-alpha2a and megestrol acetate maintenance therapy, was reasonably well tolerated. The complete and overall response rates and duration of remission and survival appear to be similar to those generally obtained with EP alone in similar patients.

Vasculitis is characterized by inflammatory changes and necrosis of blood vessels. Involvement of arteries and veins of diverse sizes throughout the body is possible and results in a multiplicity of clinical manifestations. Primary and secondary forms of vasculitis exist. Secondary vasculitis has been linked to several processes, including infections, drugs, and allergic, rheumatologic, and neoplastic disease. The majority of patients with malignant neoplasm-associated vasculitis who have been described had hematologic neoplasms. We report a patient with adenocarcinoma of the colon and vasculitis and review the 36 cases of vasculitis in patients with solid tumors documented in the world literature. The most common malignant neoplasms were non-small-cell lung cancer and prostate, breast, colon, and renal cancer. Cutaneous leukocytoclastic vasculitis and nerve and muscle microvasculitis were the most frequently observed vasculitic subtypes. Importantly, in 71% of the cases, manifestations of vasculitis appeared before or concurrent with the initial recognition or the relapse of the tumor. Management strategies that met with success in at least half the patients in whom they were used included corticosteroids, cyclophosphamide, and treatment of the underlying cancer. Prognosis may be primarily related to the ability to control the malignant neoplasm, as most of the patients who died did so because of tumor progression.

Based on encouraging in vitro and in vivo data, 14 consecutive patients with measurable metastatic previously untreated colorectal carcinoma were treated with a combination of intravenous etoposide and subcutaneous alpha-interferon. Etoposide was given at 60 mg/m2 intravenously on days 1-5 and alpha-interferon at 5 million units/m2 subcutaneously on days 1-5; courses were repeated every 21 days. All 14 patients were evaluable for response and toxicity. None of the patients achieved a complete or partial remission. Toxicity of this combination was moderate. Our data suggest that this combination is ineffective against colorectal carcinoma.

Abstract. Increasing evidence suggests that paraneoplastic syndromes may be mediated by tumour‐related cytokine release, although the specific factor(s) involved remain poorly defined. Colony‐stimulating factors (CSF) and interleukins (IL) promote colony growth in semi‐solid media and, when administered in recombinant form, increase blood counts in patients. However, normal serum CSF levels in individuals with physiologic blood counts and the relationship between specific serum CSF levels and paraneoplastic leukaemoid reaction are not well established. In this study, we found that normal serum levels of granulocyte‐macrophage CSF (GM‐CSF), as measured by ELISA, were generally < 55 pg ml−1; IL‐3, < 30 pg ml−1; and granulocyte CSF (G‐CSF), < 50 pg ml−1. In contrast, high levels of GM‐CSF (132 pg ml−1), but not G‐CSF or IL‐3, were found in a patient with a transitional cell carcinoma of the renal pelvis and increased leukocytosis correlating with the tumour burden. The GM‐CSF was biologically active, as demonstrated by its ability to stimulate colony growth in vitro. Based on these results it appears that autonomous production of GM‐CSF is one possible pathophysiologic mechanism underlying leukaemoid reaction in cancer patients.