bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase I/II trial of weekly docetaxel and cisplatin for locoregionally recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN)
Authors: Chia S. , Laskin J. J. , D’Aloisio S. , Vinduska B. , Webster M. , Kangarloo S. B. , Hao D.
Published: March 2020

15523

Background: Docetaxel and cisplatin are both active agents in the treatment of advanced SCCHN. In phase II trials the combination of docetaxel and cisplatin delivered on a 3 weekly schedule in recurrent/metastatic SCCHN demonstrated response rates (RR) of 33–46%, however it is associated with significant morbidities and treatment related mortalities. In a phase IB trial design we sought to determine the maximal tolerated dose (MTD) and the recommended dose for weekly docetaxel and cisplatin to further study in a phase II trial. Methods: Patients with measurable locoregionally recurrent and/or metastatic SCCHN with no prior chemotherapy for advanced disease were eligible. Four dose levels were planned, starting with docetaxel 25 mg/m2 and cisplatin 20 mg/m2 weekly (dose level 1) to docetaxel 35 mg/m2 and cisplatin 25 mg/m2 (dose level 4) for three consecutive weeks followed by a one week break (=1 cycle). Pharmacokinetics (PK) were performed during cycle 1 and 2. Response was assessed following every 2nd cycle. Patients were followed for safety, tolerability, duration of response and survival. Results: 16 patients were enrolled from Aug 2003-Oct 2005. 80% were male, median age 61 years (36–72), median PS 1 (0–2), 30% had prior platinum exposure as a radio-sensitizer, and two-thirds had metastatic SCCHN. MTD was not achieved with dose level 4. Median number of cycles delivered was 3 (1–6) with no significant dose reductions or delays. No G3/4 hematological toxicities or febrile neutropenia was seen across all the dose levels. One G3 dysphagia, one G3 emesis and three G3 metabolic toxicities were seen. There was no treatment related deaths. 1 CR, 2 PR and 7 stable diseases were seen with a median duration of response/stable disease of 3 months (2–19). Conclusions: Combination weekly docetaxel and cisplatin is a well tolerated and active regimen in recurrent/metastatic SCCHN. The recommended dose is docetaxel 35 mg/m2 and cisplatin 25 mg/m2 (3 consecutive weeks out of 4) in the planned phase II trial.

[Table: see text]
Safety and efficacy of the combination carboplatin and paclitaxel in patients (pts) with recurrent head and neck squamous cell carcinoma (HNSCC)
Authors: Ferrari D. , Rocca A. , Oldani S. , Zannier F. , Tartaro T. , Carbone C. , Codecà C. , Calabrese L. , Chiesa F. , Foa P.
Published: March 2020

15534

Background: Pts with recurrent HNSCC have a dismal prognosis; treatment options are poorly effective and burdened with toxicity. In this clinical setting, cisplatin and paclitaxel have demonstrated activity despite relevant side effects. The purpose of this phase II trial was to investigate whether a combination of carboplatin and paclitaxel could offer a better toxicity profile without affecting efficacy. Methods: Pts with bi-dimensionally measurable disease, previously treated with induction chemotherapy (Cisplatin and 5-FU) followed by concomitant chemo-radiotherapy, were studied. Treatment consisted of Carboplatin AUC 5 and Paclitaxel 175 mg/m2 intravenously every 3 weeks. G-CSF and darbepoetin alpha were allowed in case of neutropenia (N < 1000/mm3) or anemia (Hb < 11 g/dL). Pts were evaluated for toxicity and response. Results: So far, 15 pts were enrolled. Median age was 53 yrs; ECOG P.S. was 0–1. Site of disease at relapse was head and neck excluding lips and sinus; 12 out of 15 pts had stage IV disease. All pts were evaluated for response and toxicity. After three cycles of chemotherapy, we observed 1 complete response (6.6%) and 7 partial responses (46.6%), with a 53.2 % overall response rate (95% CI 26.6–78.7%). Stable disease was seen in 2 patients (13.3%) and progressive disease was observed in 5 pts (33.3%). Toxicity was mild: we recorded 1 case of G3 toxicity (neutropenia) and no G4 side effects. Three pts experienced G1–2 neuropathy and 4 pts G1–2 hematologic toxicity (neutropenia and thrombocytopenia). Conclusions: The current regimen was feasible and effective. The combination of Carboplatin and Paclitaxel was well tolerated and could be safely administered to pts with recurrent HNSCC as second line treatment. Enrollment and data collection are still ongoing.

No significant financial relationships to disclose.
Intra-carotid chemo (ICC) followed by radiation (RT) with concomitant temozolamide (TMZ) and subsequent maintenance TMZ therapy in patients (pts) with glioblastoma multiforme (GBM)
Authors: Mohin G. , Davis R. , Meek A. , Rosiello A. , Roque C. , Hentschel P. , Roche P. , Manzione J. , Vacirca J. , Madajewicz S.
Published: March 2020

1554

Background: Glioblastoma multiforme is one of the most resistant malignant tumors. Surgery provides only temporary, palliative relief. Radiation therapy affords additional, though short, benefit. Systemic, intravenous and/or oral chemotherapy with nitrosoureas and TMZ, increases survival only slightly. Median survival (MS) after all these modalities incorporated remains unimpressive, less than 14 months. Intracarotid chemotherapy with cisplatin and VP-16, a standard treatment at Stony Brook University Hospital since 1999, prior to RT, results in MS of 20 months. A year later we added TMZ as a part of standard treatment with or without ICC in patients with GBM. Provided here is a retrospective analysis of the treatment consisting of surgery, ICC, RT with concomitant TMZ followed by 2 years of TMZ maintenance. Methods: Fifteen patients with pathologically confirmed, newly diagnosed GBM were treated from year 2000 to 2005; 11 men; median age 53 (range 25-68); 80% with PS over 70. They underwent a surgical procedure (5 near total) followed by ICC with cisplatin 60 mg/m2 and VP-16 40 mg/m2 every 3 weeks for total of 3 cycles. Subsequently they received TMZ 75 mg/m2/day orally, concomitantly with RT 6120–6300 cGY, followed a month later by maintenance therapy with TMZ 200 mg/m2/ daily for 5 days out of each month for 2 years or until progression. Results: Fourteen pts.are being evaluated (one too early), all have survived at least 12 months.One-year PFS is 79%. Median time to progression is 19.5 months; MS is 25 months with a range of 12-48 months. Toxicity is limited to nausea and vomiting mainly grade 1-2; only 1 patient experienced grade 3 vomiting with subsequent TMZ maintenance dose reduction by about 10%. Conclusions: Surgery followed by ICC, then combination of RT + TMZ followed by maintenance TMZ therapy seems to be more effective in improving patient survival than surgery, ICC and RT as reported previously by us in pts with GBM (Cancer 2000; 10:2350–6). This treatment has been well tolerated.

No significant financial relationships to disclose.
Retrospective review of locally advanced head and neck cancer treated with concomitant chemoradiotherapy at the Miami VA Medical Center
Authors: Robles C. , Vale C. , Dinh V. , Savaraj N. , Spector S. , Chua L. , Bustillo P. , Furst A.
Published: March 2020

15541

Management of Stage III or IV Head and Neck (H&N) cancer is debatable. Standard of care is Radical Surgery (Sx) followed by Radiotherapy (XRT). However, cosmetic and functional complications are distressing and result in decreased quality of life. Therefore, organ preservation has become important when deciding best management. The VA larynx study, the EORTC 24891 and the 91–11 US intergroup trial have shown efficacy of organ preserving chemoradiotherapy (Cx+Rx) comparable to Sx and XRT. These studies are limited to laryngeal and hypopharyngeal cancers and whether same principles can be applied to other H&N sites is unknown. We conducted a retrospective study of stage III & IV H&N cancer treated at our Institution between 1996–2004 to evaluate survival, organ preservation and toxicities. 45 males between 47 to 83 years (median 59.6) were studied. 87% were white and 13% black. 82% had history of tobacco and alcohol abuse, 4% tobacco only, 11% alcohol only and 2% never smoked or drank. The sites of disease were: nasopharynx 1 (2%), oropharynx 19 (42%), base of tongue 10 (22%), larynx 6 (13%) and pharynx 9 (20%). 15 patients (33%) where stage III and 30 (67%) stage IV. The treatment was combined Cx+Rx. The mean dose of XRT was 6697 Cgy and mean cycles of chemotherapy (Cx) were 2.2. Of those, 42 patients (93%) received cisplatin and 5FU, 2 (4%) carboplatin and 5FU and 1 (2%) carbo only. 10 patients (22%) received additional Cx and 14 (31%) underwent additional Sx (neck dissection). 19 patients (42%) are alive, 19 (42%) are death and 7 (16%) were lost to f/u. Median survival is 30.6 months. 1 patient was refractory and 6 relapsed in less than a year. Among them, 4 were local relapses, 1 a neck recurrence (no prior dissection) and 1 a distant relapse. The most common acute toxicities were: Anemia 87%, neutropenia 64%, hyperglycemia 82%, transient elevation of BUN 60% and creatinine 36%, hypo/hypernatremia 64%, severe mucositis 71%, weight loss 76%, N/V 47% and severe dysphagia 27%. Cx+Rx appears to be a safe, feasible and comparable alternative to Sx regardless of the anatomical origin in locally advanced H&N cancer, with the advantage of organ preservation. Additional XRT boost, Cx or Sx could decrease relapses. Further studies are warranted to validate these hypotheses.

No significant financial relationships to disclose.
Phase I trial and pharmacokinetic study of oral gimatecan in adults with malignant glioma
Authors: Hochberg F. H. , Supko J. , Amato A. , Salem N. , Carminati P. , Wen P.
Published: March 2020

1559

Background: Gimatecan (GT) is an orally available camptothecin analogue with potent preclinical antitumor activity. A phase I trial was conducted to determine the maximum tolerated dose (MTD), toxicity profile, and pharmacokinetics (PK) of GT in patients (pts) with recurrent malignant glioma. Methods: GT was given orally once daily for 5 days every 28 days. The starting dose, 1.6 mg/m2 over 5 days, was independently escalated in pts who were and were not concurrently receiving enzyme inducing antiseizure drugs (±EIASD). PK samples were obtained up to 24 after dosing on day 1 and 168 h after dosing on day 5 of cycle 1. Results: A total of 43 pts were enrolled, 18 in the +EIASD arm and 25 in the -EIASD arm, with a median age of 51 years (range, 23–70) and median KPS of 80 (range, 60–100). All pts had prior irradiation and 84% had prior chemotherapy. Dose levels evaluated were 1.6, 3.2, 5.3, 8.0, 11.2, and 15.0 mg/m2 in the +EIASD arm and 1.6, 3.2, 5.3, 6.1, and 8.0 mg/m2 in the -EIASD arm. No dose-limiting toxicities (DLTs) occurred during 49 cycles of therapy in the +EIASD arm with dose escalation terminated at 15.0 mg/m2. Grade 3–4 myelosuppression was the DLT in the -EIASD arm, occurring in 1/11 pts at the MTD of 6.1 mg/m2, and 2/3 pts at 8.0 mg/m2. Gastrointestinal disorders, the most common side effects, were grade >3 in only 7% of pts. Pts in the +EIASD arm received a median of 6 cycles of therapy and there were 2 partial responses and 6 pts with stable disease. Pts in the -EIASD arm received a median of 2 cycles of therapy and 11 pts had stable disease. GT exhibited linear PK. EIASDs significantly affected the PK, decreasing the biological half-life 2-fold from 53 ± 25 to 25 ± 12 h (mean ± SD) and increasing the apparent oral clearance (CL/F) nearly 5-fold from 1.3 ± 1.7 L/h to 6.2 ± 4.3 L/h. CL/F was independent of body surface area. Conclusions: The MTD of GT for pts not receiving EIASDs is 6.1 mg/m2 and an MTD was not established for pts receiving EIASDs due to practical limitations on dose administration. Median duration of disease stabilization or response was 6 cycles for 44% of +EIASD pts and 2 cycles for 44% of -EIASD pts.

[Table: see text]
Phase II trial of irinotecan (CPT-11) and radiation followed by irinotecan and BCNU in glioblastoma patients (pts)
Authors: Ballman K. V. , Jaeckle K. A. , Schomberg P. , Giannini C. , Galanis E. , Brown P. , Arusell R. , Reid J. , Hammack J. , Buckner J.
Published: March 2020

1562

Background: Prior studies have shown additive effects of CPT-11 in combination with BCNU, and radiosensitizing effects of CPT-11 in gliomas. Methods: All pts had GBM by central review prior to registration. With MTD based on a pilot study (Arm A), those not receiving anticonvulsants (non-EIAC, Arm C) received RT with concomitant CPT-11 (125 mg/M2/wk × 4, cycle 1), followed by BCNU (100 mg/M2 q 6 wk) + CPT-11 (75 mg/M2/wk × 4, q 6 wks, cycles 2–5) beginning within 4 wks of RT. Pts on EIAC (Arm B) received CPT-11 (400 mg/M2/wk × 4, cycle 1) during RT, then post-RT BCNU (100 mg/M2 q 6 wk) + CPT-11 (400 mg/M2/wk q 6 wks, cycles 2–5). Dose de-escalations (but no escalations) were allowed. Toxicity was graded by CTC v. 3.0. Primary endpoint was overall survival at 12 mo (OS12), with a interim futility analysis after 12 mos. follow up in the first 35 patients. 18 “successes” (survival > 12 mo) were required to proceed. Results: There were 56 pts treated (20 Arm A, 12 Arm B, 24 Arm C). Six pts on Arm A developed toxicity at the pilot CPT-11 cycle 2–5 dose of 125mg/M2, requiring reduction (75 mg/M2) for the remainder of Arm A and all Arm C pts. The decision rule for the first 35 patients was not met, with inclusion of the 6 Arm A pts (14 successes, 19 failures, 2 incomplete data) or without these pts ( 13 successes, 20 failures, 2 incomplete). In the 35 pts with mature data, the best confirmed response was PR in 2 (6%), REGR in 4 (11%) and stable (>4 wks, STAB) disease in 7 (20%). For the 56 pts (51 with mature data), PR, REGR and STAB were noted in 4%, 16%, and 39% respectively. Reason for end of treatment (N=56) was: completion of study treatment (13%); pt refusal (11%); adverse event (9%); progression (39%); all cause death (9%); too early (13%) or other (7%). In the 51 pts whose data is mature, progression free survival at 6 mos (PFS6) was 29.8% (95% CI: 19.1, 46.3); PFS12 was 16.5% (95% CI: 8.3, 32.9) and OS at 12 mos was 45.4% (95% CI: 32.7, 63). Overall median survival was 10.7 mos (95% CI: 7.8, 14.5). Conclusions: Although limited activity (PR+REGR+STAB) of this combination was demonstrated, the decision rule (minimum OS12 “successes”) was not reached, and tolerability of this regimen was only moderate. We consider the regimen as not superior to results obtained with other regimens in prior NCCTG studies.

No significant financial relationships to disclose.
Phase II study of the combination of thalidomide and irinotecan in patients with recurrent anaplastic gliomas not on enzyme inducing anticonvulsants
Authors: Puduvalli V. K. , Giglio P. , Groves M. D. , Hess K. R. , Gilbert M. , Mahankali S. , Hsu S. , Colman H. , Conrad C. , Levin V. A. , Alfred Yung W. K.
Published: March 2020

1564

Background: Patients with recurrent anaplastic glioma (AG) have few treatment options after initial alkylating agent therapy. In this study, the efficacy of thalidomide and irinotecan against recurrent AG was tested to assess if synergistic activity of cytotoxic and antiangiogenic agents could affect clinical outcome. Methods: Patients with recurrent AG with a KPS≥70 not on enzyme inducing anticonvulsants and with fewer than three relapses after radiation therapy and chemotherapies were eligible; the total planned enrollment is 39 patients. Irinotecan is administered at 125 mg/m2 weekly for 4 weeks followed by 2 weeks rest; thalidomide is initiated at 100 mg daily and escalated weekly up to 400 mg daily. Warfarin (1 mg) is given for prevention of venous thromboembolism (VTE). Patients undergo clinical and radiologic evaluations every 6-weeks. The primary endpoint is progression free survival at 6 months (PFS-6). To determine possible radiologic correlates to treatment effects, DCE- MR perfusion-imaging studies are obtained at baseline and subsequent follow up visits. Results: 17 are evaluable for response; the remainder were inevaluable. All evaluable patients had previously failed temozolomide and 9 had also failed nitrosourea therapy. The median age is 44 yrs and median KPS is 90. Four patients are alive and progression free at 6-months whereas 9 have progressed; the median progression free survival is 23 weeks and the PFS-6 is 34%. The best response was a CR in one patient, PR in 2 and stable disease in 9. Two patients have died of unspecified causes probably related to treatment. Median overall survival has not been reached; the 12-month and 18 month survivals by Kaplan Meier analysis are 73% and 26% respectively. Grade 3 and 4 toxicities included fatigue (29%), leukopenia (29%), nausea/vomitting (24%), and diarrhea (18%) requiring dose reductions. Two patients had VTE. Conclusions: The preliminary results of this ongoing study suggest that the combination of irinotecan and thalidomide has activity in patients with recurrent anaplastic gliomas; the ongoing assessment of this combination in patients with AG will more definitively define whether the combination can be an effective second line therapy for this population.

[Table: see text]
Use of modified PCV chemotherapy as principal therapy for adults with incompletely resected or recurrent low-grade glioma: A retrospective review
Authors: Arenson E. B. , Bank J. , Pierick M. , Greenwald C. , McVicker J. , Elliott J. P. , Day J. D. , Fullagar T. M.
Published: March 2020

1571

Background: In order to assess outcomes of patients treated with chemotherapy versus a more standard approach of radiotherapy (RT), we reviewed 48 patients with newly diagnosed, partially resected or recurrent low-grade glioma (LGG) treated between 1996 and the present. Methods: Patients were divisible into three groups: those treated with chemotherapy ± RT before (Group A, 28 patients) or after (Group B, 13 patients) radiographic progression, and those with recurrences after treatment with RT (Group C, 7 patients). Diagnoses included astrocytoma (23%), oligodendroglioma (48%) and mixed glioma (29%). 39 patients were treated with chemotherapy alone and 9 received post-chemotherapy RT. Chemotherapy consisted of PCV in one case; all other patients received modified PCV (MPCV) which variably included addition of carboplatin (200–360 mg/m2) and etoposide (150 mg/m2) and substitution of temozolomide (150 mg/m2 × 5 doses) for procarbazine. The intent was to treat monthly for one year. Results: Patients received a mean of 10 courses of MPCV; 481 cycles were given. There were no deaths or admissions during chemotherapy. Grade III/IV toxicities occurred in 108 cycles (25 patients), 107 hem. and 1 GI. Late events included 1 case of MDS and 1 AML. There were no cases of disease progression during chemotherapy. Two patients stopped MPCV early, one because of worsening seizures (2 cycles) and one by personal preference (1 cycle); both died of disease. With median follow-up of 46 months (range 4–120) from initiation of chemotherapy, overall survival and progression-free survival were 89% and 79% for Group A, 91% and 83% for Group B, and 100% and 86% for Group C. Of 7 patients (15%) who recurred after completing chemotherapy, 2 have died; both had received post-chemotherapy RT and had clinical features of GBM. Four patients are either lost to follow-up (2) or alive with stable disease (2) following additional treatment. Conclusions: 1. MPCV is a tolerable regimen which can be given more aggressively than standard PCV. 2. There is minimal risk of early disease progression with MPCV. 3. Results support a prospective trial comparing MPCV to RT in patients with progressive unresectable LGG, and use of MPCV as salvage therapy for patients who fail RT.

No significant financial relationships to disclose.
An analysis of adjuvant temozolomide plus radiotherapy vs radiotherapy alone in a single academic institution
Authors: Hopkins S. , Gertler S. , Nicholas G.
Published: March 2020

1575

Background: The NCIC CE.3/EORTC 22981/26981 was open during the time period of August 2000 to March 2002. When the study closed, there existed a gap in care that did not address the ongoing management of patients (pts) with glioblastoma multiforme (GBM) that had been surgically excised. As a result of this gap, it was decided that the adjuvant use of temozolomide (TMZ) was to become the standard of care at our centre due to its lack of perceived toxicities and early evidence for its activity. Methods: An analysis was performed of all pts with GBM that were seen at the centre from 1998 to the summer of 2005. In total, 240 pts were identified across multiple medical and radiation oncologists. 75 pts were treated with radiotherapy (RAD) alone post surgery, 86 pts were treated with RAD + TMZ post surgery, 18 pts only had surgery and the remaining pts were unresectable. Average age was 59.7 years for pts treated only with RAD, and 54.6 years for those treated with TMZ + RAD (p = 0.028). 59% of pts treated with RAD were male, while 62% treated with RAD + TMZ were male. Median follow-up was 11.3 months for RAD and 15.7 months for TMZ + RAD (p = 0.0001816). Preliminary survival analysis demonstrates a 56% reduction in the risk of death for pts treated with TMZ + RAD when compared to RAD (log rank p = 9.6 × 10−6). Median survival was 12.7 months for pts treated with RAD and 27 months for pts treated with TMZ + RAD (see table ). A further analysis including recursive partitioning analysis (RPA) and duration of therapy post RAD will be attempted to confirm the similarities between the two groups. Conclusion: Adjuvant TMZ + RAD has increased overall survival by 14.3 months in our institution. Further analysis is necessary to determine the impact on duration of therapy of TMZ.

[Table: see text]

[Table: see text]
Are trends in recruitment of older patients in clinical trials (CT) changing?
Authors: Garcia M. , Perez X. , Saldaña J. , Cardenal F. , Germà J. R.
Published: March 2020

16007

Background: It has been widely reported that older patients are underrepresented in CT. This barrier has been extensively studied and some efforts have been made to increase older patient participation. This study was performed to characterize and evaluate the enrolment of elderly patients in CT in a cancer centre (Barcelona, Spain). Methods: A database-based analysis of patients entered in CT of any cancer type in a single institution between 1998 and 2005 was performed. (1) During the first 6-month period in 2005 we selected opened age-unspecified trials (AUT). Rates of patients of 74 Y entered in those trials (between 2001–2005) were analysed and compared with the corresponding rates on target population (new patients seen in Oncology Department in the first 6-month period in 2005). (2) Averages of age of CT patients in two periods of time: 1998–1999 and 2004–2005 were compared. Chi-squared and T-student analyses were used. Results: 2029 patients were entered in CT between 1998–2005. There were 1006 FTSP patients during the first 6-month period of 2005. The number of patients entered in AUT (19 trials among 71 opened [27%]) between 2001–2005 was 277. Table 1 summarizes the data by age groups. Statistically significant differences were found only between >74 y patients in CT and FTSP populations. Average age was 57.4 during 1998–1999, and 60.5 during 2004–2005 (p: 0.004). Conclusions: The number of patients >74 Y accrued in CT in a single cancer centre has clearly increased over time, maybe due to the rise of life expectancy, better patient care and the efforts in improving recruitment rates. In spite of the increase, this patient population remains underrepresented in general cancer CT.

[Table: see text]

No significant financial relationships to disclose.
Development of an information technology system to assist oncologists in daily clinical practice
Authors: Fasola G. , Puglisi F. , Aprile G. , Belvedere O. , Follador A. , Pattitoni C. , Russo S. , Sacco C. , Zanier L. , Mansutti M.
Published: March 2020

16028

Background: Daily documentation and maintenance of medical record quality is a crucial issue in oncology. Computerization can offer many advantages, but needs training and motivation of operators and fitting of clinical processes and administrative rules to technological requirements. The electronic medical record (EMR) system, a software application for the entry, retrieval, and display of patients information into a digital database, could quantitatively and qualitatively improve medical recording. Methods: We developed an application system, named G2-clin, including EMR and computerized physician order-entry (CPOE). It was integrated into the hospital information system, for documentation and therapy planning to support physicians in daily clinical practice. G2-clin was developed by internal committee of oncologists, nurses and computer scientists, with an assured information technology during the learning curve and over the years. After training, staff physicians and nurses have routinely used the G2-clin starting on March 2002. Medical records collect all data concerning management of inpatient and outpatient care. Results: To date, 317 chemotherapy protocols are available in the CPOE pick list, including experimental regimens. In 2005, G2-clin registered 1550 new patients, with 7730 chemotherapy courses and was able to provide the following data: drug storage, administration and safety procedures, assessment of adverse events according CTC, specific patient safety policies, monitoring of resources and costs, data analysis for clinical research. Main benefits are improvement of the quality of patient care and safety, practice standardization, decrease in the risk of therapy ordering errors. The main drawbacks are inhibition of patient-physician interaction and visit time extension. Conclusions: According to our pilot experience, G2-clin successfully satisfied requirements of procedures standardization and allowed distribution of accurate data to all operators. Moreover it has been useful in monitoring outcomes of care, effectiveness, efficiency, adherence to clinical practice guidelines, resources and costs.

No significant financial relationships to disclose.
The burnout syndrome among Brazilian medical oncologists
Authors: Glasberg J. , Horiuti L. , Novais M. , Canavezzi A. , Miranda V. , Chicoli F. , Gonçalves M. , Bensi C. , Del Giglio A.
Published: March 2020

16038

Background: The burnout syndrome (BNS) is prevalent among oncologists and is characterized by three components: emotional exhaustion, depersonalization and low personal accomplishment. BNS is associated with depression anxiety and impaired job performance. We aimed at evaluating the prevalence of BNS among brazilian medical oncologists and the variables that correlate with its presence. Methods: We sent three questionnaires (general, Maslach burnout questionnaire and an opinion survey) to the 458 members of the Brazilian Society of Medical Oncology (SBOC) and we attempted to increase the amount of answers by an email recall to all members. In order to evaluate correlations between variables we used Fisher, Chisquare and ANOVA tests, and considered significant only p values lower than 0.05. We used logistical regression to conduct multivariate analysis, having the presence of BNS as a dependent variable. Results: The response rate was 22.3%. When asked if they would choose oncology as a career again, 90 (88.25%) answered affirmatively. According with the criteria proposed by Grunfeld, that considers BNS present when at least one dominion is severely abnormal, the incidence of this syndrome was 68.6% (95% CI: 58,68% to 77.45%). By univariate analysis, we observed a negative significant correlation of BNS with having regular physical activity and/or a hobby, reporting to have a religious affiliation and with willingness to choose oncology as a career again. We found a positive significant correlation of BNS with living together with someone and reporting vacation time as insufficient. By multivariate analysis having a hobby/physical activity, a religious affiliation, living with a companion and rating vacation’s time as sufficient were all correlated significantly and independently with BNS. Conclusions: BNS is prevalent among brazilian medical oncologists, nevertheless most of them would choose medical oncology as a career again. To have a hobby and/or a regular physical activity, enough time of vacations and a religious affiliation correlate negatively with the presence of BNS and are potentially modifiable preventive measures to decrease the frequency of this syndrome.

No significant financial relationships to disclose.
A phase 1 trial of a novel organic arsenic S-dimethylarsino-glutathione (ZIO-101) in hematological malignancies
Authors: Kornblau S. M. , Jackson C. E. , Worthing A. , Faderl S. , Beran M. , Fayad L. , Ravandi-Kashani F. , Bothakur G. , Gale R. , Verstovsek S.
Published: March 2020

16503

Background: Inorganic Arsenicals (IA, e.g. AS2O3) kill many human leukemia cell lines and have efficacy in APL. Evaluation of efficacy against other types of leukemia is limited by the substantial toxicity of IA. Organic Arsenicals (OA) are less toxic than IA. ZIO-101 (S-dimethylarsino-glutathione) is an OA with activity against diverse cancers in in vitro tests and animals mediated through mitochondrial damage and apoptosis induction. ZIO-101 may induce apoptosis by different mechanisms than As2O3 and can kill As2O3-resistant cancer cells. Compared to As2O3, the LD50 of ZIO-101 in mice is 50X higher and at equimolar extracellular arsenic concentrations ZIO-101 produces 15× higher intracellular arsenic concentration. These features make ZIO-101 attractive for evaluation in leukemia. Methods: A phase-1 study evaluating the safety and pharmacokinetic (PK) profile of ZIO-101 in subjects with advanced hematological malignancies is underway. 8 patients (PATS) with acute myelogenous leukemia (AML) (median 3 prior treatments) received ZIO-101 at doses of 78, 109 or 153 (n = 4, 3, 1) mg/m2/d IV for 5 d every mo. Results: Therapy with ZIO-101 has been safe and well-tolerated. Toxicities ≥ grade-2 included hyperglycemia (N = 3) and decreased albumin (N = 3) and Ca (N = 3) and 1 subject each had ≥ grade 2 elevations in LFT, or decreases in K, or PO4, febrile neutropenia and rash. Preexisting anemia and thrombocytopenia increased by 1 grade in 4 and 3 PATS each. Grade ≥3 neutropenia occurred in 2 PATS. No significant renal, liver or heart toxicity occurred, 1 patient with prior 10AV block had transient prolongation of QT interval non-recurring on rechallenge. PK studies at 109 mg/m2/d showed a tmax = 1.5 h (SD ± 0.7 h), Cmax = 402 ng/mL (±33 ng/mL), t1/2 = 14.4 h (±2.9 h) and AUC0-∞ = 8.93 μg · min/mL (±1.82 μgzmdmin/mL). 4 PATS progressed after 1 cycle, 3 had stable disease and received a 2nd cycle: 1 progressed and 2 remain on study. 1 patient is too early to evaluate. Blood myeloblasts decreased (9 to 1.1 × 10e9/L at day 13) in 1 subject and completely resolved in 2 (pre-therapy: 100 and 336 × 10e9/L). Bone marrow myeloblasts were unchanged. Conclusions: Administration of ZIO-101 to PATS with advanced AML was safe and dose-escalation continues and a modest antileukemic effect has been observed.

[Table: see text]
Evaluation of efficacy of serum and broncho-alveolar lavage Galactomannan estimation by ELISA in high-risk persistent febrile neutropenic patients
Authors: Sengar M. , Kumar L. , Thulkar S. , Kochupillai V.
Published: March 2020

16505

Background: Chest infections constitute 36% of all infections in our acute leukemia patients. Conclusively establishing the diagnosis of invasive fungal aspergillosis (IPA), an important cause pulmonary infiltrates and mortality in high-risk febrile neutropenic patients, however, is difficult. We therefore evaluated the value of ELISA for Galactomannan (Gm) antigen and correlated the results with radiological findings. Methods: Twenty patients with persistent high-risk febrile neutropenia were assessed with chest X-ray, high resolution computed tomography (HRCT) chest and bronchoalveolar lavage (BAL) from the affected segment on day 5 of fever. Microbial cultures of blood, sputum and BAL and Galactomannan estimation in serum and BAL were done. IPA was defined as per the Mycoses Study Group criteria. Sensitivity, specificity and negative and positive predictive value of Galactomannan assay and diagnostic yield of each investigation was determined. Results: Diagnostic yield of CXR was 10%, blood culture, mainly gram negative bacilli, 15%, and BAL 20% (Aspergillus - 10%). Based on microbiology, radiology and cytopathology IPA was diagnosed in 16 cases (proven -1, probable -2, possible -13) and miliary tuberculosis, bacterial pneumonia and nocardiosis constituted the remaining. Nodules and halo sign were the most frequent (60%) CT findings in IPA. Sensitivity, specificity and positive and negative predictive value for serum were 78%, 100%, 100% and 64%, respectively, and for BAL, were 87.5%, 100%, 100% and 75%, respectively. Conclusions: CT-guided BAL and serial serum GM estimations are valuable non-invasive screening tools for IPA in high-risk persistent febrile neutropenic patients.

No significant financial relationships to disclose.
Long term follow up after treatment of hairy cell leukemia with 2-CdA
Authors: Ramzi M. , Haghshenas M.
Published: March 2020

16518

Background: Hairy cell leukemia (HCL) is a chronic B cell disorder that follows an indolent but progressive course. The ability of new purine analogue deoxyadenosine to induce long lasting complete remission in patients with hairy cell leukemia has revolutionized the treatment of this disease. We report the long term outcomes of patients with HCL treated in Shiraz, in south of Iran,with this drug. Methods: Between October 1993 till April 2004, 79 patients with classic symptomatic hairy cell leukemia were treated with 2-cholorodeoxy adenosine (2-CdA) with dose of 0.1 mg/kg of body weight per day by continuous intravenous infusion for 7 days. Results: sixty nine (87%) of patients achieved an initial complete response and 10 (12.6) a partial response with an overall median duration of response follow up of 78 months. Five patients had relapsed at a median of 43 months. All of 5 patients after relapse treated with second courses of 2-CdA, 4 (80%) achieved second complete responses and one (20%) partial response. In our study we had not any case of second malignancy after treatment with 2-CdA with median follow up of 82.5 months. Conclusion: This study confirms single course of 2-CdA induced long lasting complete response in the vast majority of patients. Relapse rate for complete responders were low. Patients who relapse can be successfully retreated with this drug, so we conclude 2-CdA had high efficacy and a favorable acute and long term toxicity profile in our patients in south of Iran, without any increase in risk of second malignancy.

No significant financial relationships to disclose.
Staging of small cell lung cancer (SCLC): Comparison of two criteria by survival analysis
Authors: Williams R. , Eskandari N. , Kendall A.
Published: March 2020

17030

Background: Consistent staging of SCLC is pertinent to the selection and evaluation of treatment regimens. The Veterans Administration Lung Study Group (VALG) defines patients with limited disease (LD) as those with tumor limited to one hemithorax. In contrast, the International Association for the Study of Lung Cancer (IASLC), basically a TNM method, defines limited disease as those with no distant metastases. We assessed the survival of intermediate patients (ID), defined as those who qualified as LD by the IASLC but not the VALG criteria. Methods: A retrospective chart review was done on 252 patients consecutively diagnosed with SCLC between 1990 and 2004 at a Northern California hospital. Kaplan Meier analysis and log-rank tests were used to compare the survival of ID and LD patients. We also compared survival of both ID and LD to patients with extensive disease (ED). Multivariate Cox regression analysis was used to incorporate clinically relevant data. Bonferroni adjustment was made for multiple comparisons. Results: We defined 93 patients as LD, 32 as ID and 127 as ED. Median survival of patients with ID was 12 months (95% CI 9–16 months) and for LD 11 months (95% CI 9–13 months). Median survival for patients with ED was 6 months (95% CI 4–7 months) and significantly shorter (P < .0001) than either ID or LD. Conclusions: The present study questions the inclusiveness of the VALG definition of LD concurs with prior findings from Germany (Lung Cancer 37:271, 2002). SCLC patients should be staged by the IASLC criteria when being evaluated for treatment regimens.

No significant financial relationships to disclose.
Cardiac changes on MRI and SPECT after definitive radiotherapy in patients with lung cancer
Authors: Lind P. A. , Larsson T. , Lideståhl A. , Thoren L. , Ågren-Cronqvist A. , Nygren A. T. , Brodin O.
Published: March 2020

17059

Background: To determine if lung cancer irradiation (RT) induces myocardial damage. Methods: Patients undergoing definitive RT with > 10% incidental cardiac RT (>30 Gy) were evaluated pre-RT and at 2 and 6 mos post-RT FUs. They underwent gadolinium enhanced cardiac MRI and rest-SPECT. The mean cardiac (MCD) and left ventricular (MLVD) doses were calculated on the dose planning CT. Data on confounding factors, e.g. diabetes, smoking, and levels of TGF-B, plasma glucose/fats were collected. The MRIs were analyzed for reductions in stroke volume (SV), ejection fraction (EF), left ventricular mass (LVM), and for visual signs of myocardial fibrosis/damage. The severity of SPECT-changes were analyzed with the semiquantitative summed rest score (SRS)-method (16-segments) and the extent was further quantified with the Bull’s-eye-view technique as volume-% (cutoff level for 1.5 SD below the mean). The Wilcoxon Matched Pairs test was used to study changes in repeated measurements. To test variable relation the Pearson’s Correlation Coefficient was calculated. Results: Presently, 13/30 patients are evaluated after their first FU. There was a limited decrease in LVM at first FU compared to pre-RT (median change: −6 g; P = 0.02), but no changes in SV or EF. The correlation coefficient for MCD (range: 2–32 Gy) (MLVD: 1–36 Gy) and MRI-reductions in SV, EF, and LVM at 2 mos were −0.46 (−0.27), −0.22 (−0.1), −0.30 (−0.12), respectively (P-values > 0.05). On rest-SPECT, a clinically significant SRS-increase was evident in one patient (SRS: +13; extent of defect 19%) at 2 mos. A new, extra cardial mass was, however, evident in this patient which would cause attenuation. No myocardial fibrosis/damage was detected on visual inspection of the MRIs. There was no increase in S-troponin levels at the first FU. Conclusions: At this stage of our study, no cardiac changes were evident following lung RT. This contrasts against studies in breast cancer RT were SPECT-defects corresponding to the tangential beams have been reported. RT-induced chest wall damage could in our series explain new SPECT-defects in one patient, who had no structural changes on MRI. Our entire cohort should be evaluated after both planned post-RT FUs before definitive conclusions can be drawn concerning cardiac damage and lung cancer RT.

No significant financial relationships to disclose.
A phase II trial of thalidomide (T), irinotecan (I) and gemcitabine (G) in chemonaive patients with advanced non-small cell lung cancer (NSCLC)
Authors: Jazieh A. R. , Komrokji R. , Patil S. , Flora D. , Knapp M. , Gupta A.
Published: March 2020

17068

Background: Chemotherapy with platinum based doublets provides only a modest benefit in advanced NSCLC with a median overall survival (OS) of 8 months and 1-year survival rate of 33% (Schiller JH et al, N Engl J Med 2002). We performed a phase II study to determine the efficacy of thalidomide, an immunomodulatory agent with antiangiogenic activity, in combination with chemotherapy in patients with advanced NSCLC. Methods: Chemonaive patients with stage IIIB/IV NSCLC with ECOG PS≤ 2 and adequate organ function were treated with G (1000 mg/m2) and I (100 mg/m2) IV on days 1 and 8 of a 21 day cycle. Patients also received T (200 mg orally with escalation as tolerated to a maximum of 400 mg daily). Therapeutic anticoagulation with coumadin was given to the last 11 patients. Results: Twenty four patients were enrolled: median age 57 years (41–76); M:F=17:7; ECOG PS 0/1/2=13/7/3; stage IV: IIIB= 21:3 and CNS involvement: 6. Two pts died before treatment, 1 was ineligible and 1 was lost to follow up. The remaining 20 pts received a median of 4 treatment cycles (range 1–6). The regimen was generally well tolerated and the most common grade 3–4 toxicities encountered were: diarrhea (4); pneumonia (3) and thromboembolic events (3). There were no thromboembolic events after anticoagulation was initiated. Two patients (10%) experienced partial response, 14 (70%) experienced stable disease, 1 had progressive disease. Three patients (15%) were not evaluable for response due to early withdrawal. The median OS was 10.8 months (range 0.6–37+) and 1-year and 2-year survival rates were 37% and 16%, respectively. The median time to progression was 3.6 months (range 0.2–11+). Conclusions: The combination of thalidomide and chemotherapy is reasonably well tolerated and active in advanced NSCLC as evidenced by good OS and 1- and 2-year survival rates. The addition of thalidomide to a non-platinum based regimen appears to compare favorably to the results of the traditional platinum based doublets.

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Clinical efficacy and immunogenicity of the optimized cryptic peptide TERT572Y vaccine (Vx-001) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: Kosmatopoulos K. , Bolonaki E. , Aggouraki D. , Nikoloudi E. , Kanellou P. , Papadimitraki E. , Kotsakis A. , Mavroudis D. , Georgoulias V.
Published: March 2020

17069

Background: BTERT572Y, an optimized cryptic peptide homologous to TERT induces efficient antitumoral T cell cytotoxic immunity but not autoreactivity in vivo in HLA-A*0201 transgenic mice and healthy blood donors and prostate cancer patients (J. Clin. Invest., 2004, 113,425). Moreover, it was well tolerated and effective in eliciting specific T cell immunity in patients (pts) with advanced malignancies (ASCO 2005, abstr 2579). Methods: We evaluated its clinical efficacy, safety and immunogenicity in 13 HLA-A*0201 pts with advanced, stage IIIb (7 pts) and stage IV (6 pts), NSCLC. Three pts were in stable (SD) and ten pts in progressive (PD) disease following prior therapy. The vaccination protocol consisted of two subcutaneous injections of optimized TERT572Y peptide followed by four injections of native TERT572 peptide. Both peptides were emulsified in Montanide ISA51. Results: Eight pts completed the entire vaccination program, 4 discontinued due to PD and 1 is ongoing. The median follow up is 6.5 months (range 2.0–29.9). Three of 10 (30%) pts with prior PD developed SD for 6+, 7+ and 9 months. Overall clinical response was SD in 6 and PD in 7 pts. Median TTP was 8.1 months (range 3.7–9.1) for stage IIIb and 2.3 (range 2–6.9) for stage IV pts. Minimal grade I/II primarily skin toxicity was observed. ELISPot-detected TERT572 specific CD8+ cells were demonstrated in all 7 pts tested. Conclusions: TERT572Y peptide vaccine is well tolerated and effective in eliciting a specific T cell immunity. The disease stabilization observed in 30% of pts with previously progressive disease is very encouraging and deserves further evaluation.

[Table: see text]
Feasibility report of stereotactic body radiotherapy with tomotherapy for early stage medically inoperable lung cancer using extreme hypofractionation
Authors: Hodge C. W. , Khuntia D. , Tome W. A. , Jaradat H. , Mehta M. P.
Published: March 2020

17097

Background: This is a report on the technical feasibility, dosimetric aspects, and daily image-guidance capability with megavoltage computed tomography (MvCT) imaging of stereotactic body radiotherapy (SBRT) using tomotherapy for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). Methods: Treatment planning was performed using 4D PET-CT in a BodyFix device. A pilot group of 4 patients with <5 cm T1/2, N0 tumors, was treated using IMRT (tomotherapy), utilizing daily image guidance with MvCT. Patients received 60 Gy within 10 days, delivered in five 12Gy fractions. The primary endpoint of this study was evaluation of acute and sub-acute treatment related toxicities. The secondary endpoint was radiographic evaluation for objective tumor response. Results: All 20 fractions were successfully delivered. MvCT provided excellent tumor visualization for daily image guidance. No significant tumor regression was observed in any patient during the 2 weeks of therapy, using volumetric contouring on MvCT images. The relevant dosimetric aspects, measured as median normalized total dose (NTD) were as follows: tumor = 116.5 Gy10; whole lung = 6.8 Gy3. Maximum fraction-size equivalent dose (FED) demonstrated median values as follows: esophagus = 4.04 Gy3; spinal cord = 6.53 Gy3. All patients are alive at a median follow-up of 6 months, with no grade 2 or higher acute pulmonary toxicities. Early radiographic follow-up demonstrates all 4 patients experienced a partial response. The mean tumor regression is 79% (range 64–85%). Conclusions: 4D PET-CT permits precise target delineation. In this, the first reported clinical experience, IMRT delivery of SBRT using tomotherapy is feasible, safe and free of major acute toxicities. The conformality which is obtained by helical delivery of the therapeutic dose makes it well-suited for dose escalation through extreme hypofractionation, with extremely low mean NTD to normal tissue. The ability to obtain on-treatment megavoltage CT scans to confirm tumor localization is a substantial advantage. Further studies and longer follow-up are warranted to evaluate the efficacy of this treatment modality.

[Table: see text]
A phase I trial of ABT-751 and carboplatin (C) in patients (pts) with previously treated non-small cell lung cancer (NSCLC)
Authors: Dragnev K. H. , Rigas J. R. , Disalvo W. M. , Simeone S. A. , Hagey A. E. , Gordon G. B. , Dmitrovsky E.
Published: March 2020

17098

Background: NSCLC is the leading cause of cancer mortality for men and women in the United States. More effective treatments are needed to prolong survival and improve quality of life. Platin-containing chemotherapy doublets are commonly used in NSCLC treatment. ABT-751 is a novel oral anti-microtubule agent targeting the colchicine binding site. As single agent, it was well-tolerated and showed a preliminary signal of activity in previously treated NSCLC. In vivo studies demonstrated additive activity between ABT-751 and cisplatin in a NSCLC xenograft model. Methods: A phase I trial of ABT-751 and C was conducted in pts with advanced previously treated NSCLC. Primary objective - maximum tolerated dose (MTD). Secondary objectives - toxicities, efficacy, and surrogate markers of response (cell cycle changes and cyclin D1 expression) in buccal swabs from pts at the phase II dose. Six dose levels - 1: ABT-751 100mg bid, C AUC 4.5; 2: ABT-751 125 mg bid, C AUC 4.5; 3: ABT-751 125 mg bid, C AUC 6; 4: ABT-751 150 mg bid, C AUC 6; 5: ABT-751 175 mg bid, C AUC 6; 6: ABT-751 200 mg bid, C AUC 6. ABT-751 was taken orally twice a day for 14 days in a 21 day cycle, C was administered intravenously on day 4 during cycle 1 and on day 1 on subsequent cycles. Rapid dose escalation was used for the first 3 dose levels followed by cohorts of at least 3 patients for the remaining dose levels. Results: Eight pts were enrolled, all stage IV NSCLC, 4 women, median age 62 (47–73), all KPS 80, 6 had one and 2 had 2 prior therapies. A median of 3.5 (1–4) cycles was administered. Dose-limiting toxiticies of grade 3 fatigue and grade 4 thrombocytopenia and neutropenia were observed in 2/5 patients on dose level 4. Common grade 2 toxicites were constipation and peripheral sensory neuropathy (levels 2–4). MTD was dose level 3. Seven pts were evaluable for response, 2 had partial responses (levels 2 and 4, both had one prior therapy), 4 had stable disease, 1 had disease progression. Median time to progression was 18.7 weeks (6–24+). Pharmacokinetic analyses and buccal swabs are being performed. Conclusions: The recommended phase II doses are ABT-751 125 mg twice daily for 14 days and carboplatin AUC 6 on a 21-day cycle. This regimen is well tolerated and shows preliminary evidence of activity for previously treated NSCLC.

[Table: see text]