bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tinzaparin prophylaxis against thromboembolic complications in brain tumor patients
Authors: Vredenburgh J. J. , Bohlin C. , Reardon D. A. , Desjardins A. , Quinn J. , Rich J. , Sathornsumetee S. , Marks L. B. , Friedman A. H. , Friedman H. S. 
Published: March 2020

1539 Background: Thromboembolic complications are common in brain tumor patients, contribute to the morbidity and mortality and complicate treatment. Twenty to 40% of brain tumor patients develop a deep venous thrombosis and/or pulmonary embolus during their course. Thromboembolic complications are the second leading cause of death in brain tumor patients. One of the low molecular weight heparins, tinzaparin, has increased factor Xa activity as opposed to thrombin inhibition, which may improve the therapeutic:toxicity ratio. Methods: We report a phase II trial of prophylactic tinzaparin for newly diagnosed brain tumor patients. Twenty-seven of the planned 40 patients have been accrued. Patients received daily tinzaparin at a fixed dose of 4500 IU subcutaneously beginning a minimum of 48 hours post-operatively and a maximum of 4 weeks post-operatively. Patients were scheduled to receive tinzaparin for 12 months. During chemotherapy cycles, the blood counts were monitored weekly. If the platelet count was <50,000, the tinzaparin was held until the platelets were >100,000. Results: One of the patients developed a grade 3 CNS hemorrhage, necessitating cessation of the tinzaparin, there have been no grade 4 or 5 CNS hemorrhages or treatment associated mortality. Also, there have been no ≥ grade 2 systemic hemorrhages. One patient developed a deep venous thrombosis while taking tinzaparin, and three patients developed thromboembolic complications while off tinzaparin secondary to thrombocytopenia. One patient was taken off study for increased liver function tests, possibly secondary to tinzaparin. The patients have taken the tinzaparin for 4–52 weeks, with a median of 18 weeks. Conclusions: Tinzaparin at a fixed prophylactic dose is safe and may decrease the incidence of thromboembolic complications in brain tumor patients. If the completed phase II study yields similar results, a phase III trial is warranted. No significant financial relationships to disclose.
Induced fluorescence of medullary carcinoma of the thyroid: A technology with potential to improve visualization of malignant tissue at the time of surgical resection
Authors: Johnson T. E. , Luiken G. A. , Quigley M. M. , Xu M. , Hoffman R. M. 
Published: March 2020

15503 Background: Surgery for medullary carcinoma of the thyroid can at times be technically challenging to the surgeon. Inducing the cancer cells to be fluorescent would have the potential to improve the surgeon’s ability to quickly and accurately identify and excise all of the malignant tissue. We have previously demonstrated the feasibility of induced tumor fluorescence with fluorophor-tagged anti-tumor antigen antibodies using human colon and breast cancer cell lines. We present here our results using a human medullary carcinoma of the thyroid cell line in the nude mouse model. Methods: A human medullary carcinoma of the thyroid cell line that was demonstrated to express CA 15–3 was used. Thyroid carcinoma cells were subcutaneously implanted in 4 nude mice (3 study mice and 1 control mice). Three weeks after injection, tumor nodules were easily detectable. Using the tail vein method, 3 study mice were injected with fluorophore-tagged anti-CA 15–3 and 1 control mouse with fluorophore-tagged IgG. Mice were examined using a small animal imaging system with a 470 nm light source and appropriate filters. They were also examined using a simple blue LED flashlight fitted with a fixed 470 nm band pass filter for illumination and were observed through filtered goggles. Results: Fluorescence of tumor nodules in the study mice could be seen through the skin. On dissection and exposure of the tumor nodules, this fluorescence was intense and clearly distinguishable from the surrounding normal tissue using either the imaging system or the blue LED. The control mouse injected with fluorophore-tagged IgG and examined in a similar manner revealed no tumor fluorescence. Conclusions: When tumor antigens are known, fluorophore-tagged antibody induced fluorescence is simple, easy to perform, requires no technically complex equipment or operator expertise and could be adapted to thyroid cancer surgery in the academic or community hospital setting. This technology would be indicated in those patients undergoing initial resection of medullary carcinoma of the thyroid as well as in those patients undergoing resection of recurrent disease where accurate identification of tumor tissue may be more difficult and time consuming. No significant financial relationships to disclose.
Daily concurrent chemoradiotherapy with docetaxel (D) and cisplatin (C) using new superselective intra-arterial infusion via the superficial temporal artery (HFT method) for stage III, IV head and neck cancer—Preservation of the primary lesion
Authors: Tohnai I. , Fuwa N. , Mitsudo K. , Nishiguchi H. , Fukui T. , Yamamoto N. , Ueda M. , Ito Y. 
Published: March 2020

15513 Background: We previously developed a new method of superselective intra-arterial infusion via the superficial temporal artery (HFT method; Hattori, Fuwa and Tohnai). Our previous study involved preoperative daily concurrent radiotherapy and chemotherapy with docetaxel (D) and cisplatin (C) using the HFT method for 41 patients with stage III, IV oral cancer. Clinical effects were complete response (CR) in 29 (82.9%) and partial response (PR) in 6 (17.1%) patients and pathological effects of the resected tumor were CR in 31 (88.6%) and PR in 4 (11.4%) patients, with a 5-year cumulative survival rate (overall rate) of 78.8%. Thus, the present study investigated the effectiveness of chemoradiotherapy using the HFT method without surgery for stage III, IV oral cancer. Methods: Patients (n = 16) with stage III, IV oral cancer were treated. A new catheter was prepared by modifying a 1.35-mm diameter angiographic catheter and inserting it superselectively using a guide wire to the feeding artery of the tumor via the superficial temporal artery. Long-term catheterization is possible by this method. Radiotherapy (total dose: 60 Gy) and superselective intra-arterial infusion chemotherapy using D (total dose: 60 mg/m2) and C (total dose: 100 mg/m2) were concurrently performed daily. Radical neck dissection was performed after chemoradiotherapy, but the primary lesions were preserved. Results: Toxicities over grade 3 were leukopenia (6.3%), mucositis (25.0%), and dermatitis (18.8%). No infection was associated with catherization. No major complications were observed. The clinical effects were CR in 13 (81.5%) patients, with recurrences in 3 patients. Salvage operations were performed in these 3 patients. The 3-year cumulative survival rate (overall rate) of 87.5% is higher than that of conventional therapy. Conclusions: Our HFT method, unlike the Seldinger method, allows for long-term catheterization, enabling daily concurrent chemoradiotherapy to be performed. This method promises to be the strategy of choice for the treatment of stage III, IV head and neck cancer. No significant financial relationships to disclose.
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.