bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between route of intra-CSF chemotherapy administration and efficacy of therapy in patients wtih neoplastic meningitis
Authors: Glantz M. J. , Chamberlain M. C. , Batchelor T. , Eric W. , Cavalli F. , Shapiro W. R. 
Published: March 2020

1530 Background: NM is a devastating complication of solid tumor and hematologic malignancies. Although controversial, the current standard of care for patients with this disease includes intra-CSF chemotherapy. The importance of route of chemotherapy administration, however, remains controversial. Methods: 124 patients with NM from solid tumors (100 patients) or lymphoma (24 patients) were randomized to receive either sustained-release cytarabine—the study arm; or conventional intra-CSF chemotherapy (methotrexate for solid tumor patients; non-sustained-release cytarabine for lymphoma patients)—the control arm. The route of administration (lumbar vs. ventricular) was not specified. Results: Patients in the study and control arms were well-balanced for factors of known prognostic importance, including age, KPS, and extent of systemic tumor. Progression-free survival was identical between the study and control treatment arms for all patients (35 vs. 43 days, p = 0.73), for solid tumor patients alone (35 vs. 37.5 days, p = 0.79), and for lymphoma patients alone (34 vs. 50 days, p = 0.82). When outcome was examined in solid tumor patients as a function of route of chemotherapy administration, there was no difference in progression-free survival for patients treated with DepoCyt by the ventricular vs. lumbar routes (29 vs. 43 days, p = 0.35). For patients treated with methotrexate, there was a statistically significant difference favoring patients receiving intraventricular therapy (43 vs. 19 days, p = 0.048). Conclusions: Both the pharmacokinetic profile of the intra-CSF chemotherapeutic agent and the site of administration influence the outcome of patients treated for NM. Intraventricular administration, or the use of sustained-release chemotherapeutic agents if the lumbar route is used, appears to be critical to the success of treatment. The implications of this finding may also extend to patients (e.g. those with acute leukemias, high-risk NHL, or her2/neu-positive breast cancer) receiving prophylactic intra-CSF chemotherapy since, in the prophylactic setting, intra-lumbar chemotherapy administration is almost always employed. [Table: see text]
Calculated versus measured creatinine clearance for the dosing of methotrexate in patients with primary CNS lymphoma
Authors: Gerber D. E. , Ye X. , Grossman S. A. , Batchelor T. 
Published: March 2020

1536 Background: High-dose methotrexate (HDMTX) (8g/m2), the cornerstone of therapy for primary central nervous system lymphoma (PCNSL), is commonly dosed using a measured 24-hour creatinine clearance (CrCl) every 2–4 weeks. Because these collections are cumbersome, costly, and at times unreliable, the use of a calculated CrCl was evaluated. Methods: A retrospective analysis was performed on data from all 25 patients (287 treatments) with PCNSL who participated in a multi-center phase II clinical trial of HDMTX conducted by the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium. Results: The 25 patients had a median age of 61 years (range 32–75 years). Seventeen patients (68%) were men. The patients received a median of 14 (range 2–21) HDMTX treatments. For 256 of 287 total treatments (89%), data were available to compare the measured and calculated (using the Cockcroft-Gault equation) CrCl. The average measured CrCl was 93±29 ml/min, and the average calculated CrCl was 107±43 ml/min. The correlation coefficient (r) was 0.66 (p<0.001) between the measured and calculated CrCl. Of the 256 HDMTX treatments evaluated, 158 (62%) had reliable 48-hour serum MTX levels documented. Forty-eight levels (30%) were in the ideal range (0.3–1 μmol/L), 98 levels (62%) were lower (<0.3 μmol/L), 12 levels (8%) were higher (>1–3 μmol/L), and no levels were in the range associated with significant toxicity (>3 μmol/L). Of these 158 treatments, the use of a calculated rather than measured CrCl would have yielded an identical MTX dose for 46 treatments (29%), a higher MTX dose for 62 treatments (39%), and a lower MTX dose for 50 treatments (32%). This distribution was not significantly different among the subsets of low, ideal, and high MTX levels (p=0.13). Conclusions: In this cohort of patients with PCNSL, there is a high correlation between the calculated and measured CrCl. For these patients, there is not a clear association between the method of determining CrCl and serum MTX levels. Therefore, the administered MTX doses using either method are likely to be similar. In this patient population, a calculated CrCl could be used to avoid the cost and inconvenience associated with measured CrCl. No significant financial relationships to disclose.
Phase II study of capecitabine (X) plus reirradiation in patients (pts) with recurrent squamous cell carcinoma of the head and neck (SCCHN)
Authors: Kornek G. , Vormittag L. , Burian M. , Radonjic D. , Selzer E. 
Published: March 2020

15504 Background: X has shown substantial activity in SCCHN [Pivot et al. 2004] and is replacing 5-FU as the backbone of chemotherapy in a wide range of solid tumors, particularly colorectal cancer. In addition, X has a unique survival benefit in breast cancer. There is substantial data to support using X in chemoradiation [Dunst et al. 2004]. We evaluated the therapeutic impact and safety profile of X plus reirradiation in SCCHN. Methods: Pts with locally advanced unresectable SCCHN who had prior radiotherapy (RT, with or without chemotherapy) received X 450 mg/m2 twice daily, 7 days a week. RT was delivered as a standard fractionated regimen (2 Gy/day, 5 fractions/week) up to a total dose of 50–70 Gy. The cumulative (life-time) dose within overlapping fields was not to exceed 120–130 Gy. Results: Currently, 20 male pts have completed treatment. Baseline characteristics were: median age 57 (42–72), ECOG PS 0/1 5/15. Six pts had previous chemoradiation followed by radical resection; 4 had surgery and postoperative RT; 10 had concomitant chemoradiation (accelerated and hyperfractionated). Twelve pts experienced locoregional recurrences, 4 developed secondary primaries, and 4 had a regional lymph node relapse. The median time since prior radiation therapy was 16 (8–244) months. Efficacy (as evaluated by WHO criteria): 7 pts (35%) had a complete (2) or partial (5) response; stable disease was observed in 11 pts, and tumor progression immediately after therapy was observed in 2 pts. Median duration of local control and median survival will be presented at the meeting. The most frequently observed toxicity was mucositis, which was grade 3 in only 2 pts; grade 1 or 2 skin reaction was seen in 9 pts. There was no evidence of systemic toxicity or myelosuppression, probably due to the very low dose of X. RT was completed without delay in all pts, and X was interrupted prematurely in 2 pts due to grade 3 mucositis. Conclusions: Our preliminary data suggest that X chemoradiation is a well-tolerated and effective treatment modality for previously irradiated pts with SCCHN. Based on available data, a higher dose of X should be feasible and potentially more effective. Earlier use of X in SCCHN could also be evaluated. [Table: see text]
A trial of gemcitabine (gems) in combination with cisplatin for treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC)
Authors: Yang M. , Wang H. , Wang W. , Chiou T. , Chen P. 
Published: March 2020

15505 Aims: To determine the efficacy of gemcitabine in combination with cisplatin, and to assess the safety profile of the regimen as the first-line treatment in patients with recurrent/metastatic HNSCC. Methods: An open-label, non-comparative, multi-center phase II study for patients with histologically proven recurrent/metastatic HNSCC without prior treatment for their recurrent/metastatic disease. In this trial, 1250 mg/m2 gemcitabine was administered alone on day 1 and day 8 and 80 mg/m2 cisplatin would follow gemcitabine on day 8, to be repeated in cycles of 21 days until disease progression, intolerable toxicity, or consent withdrawal. Results: Between 04/2004 and 09/2005, 34 patients were enrolled in this study. 33 patients have completed the study treatment. Characteristics of the 33 patients: male- 33; median age- 51 years (range 38–65); 30 pts had a performance status (PS) of 0 or 1 and 3 had a PS of 2 (ECOG scale); histology: recurrent/metastatic HNSCC in all cases. Of the 33 patients, 25 were evaluable for response assessment. Partial response was observed in 8, stable disease in 10, and progressive disease in 7 patients. Overall response rate was 32% (95% Confidence interval 12%–52%). Grade 3/4 hematological toxicities included neutropenia in 12 pts, leukopenia in 11 pts, thrombocytopenia in 2 pts and anemia in 8 pts. Grade 3/4 nausea or vomiting was observed in 2 pts. Other toxicity was mild in the treatment. Patient treatment and follow-up are still ongoing. Conclusion: This study, with an overall response rate of 32% and a rate of stable disease of 40%, has shown a good activity with mild and acceptable toxicities of gemcitabine/cisplatin regimen in patients with recurrent/metastatic HNSCC. Survival and response analyses will be presented at the meeting. No significant financial relationships to disclose.
AlteRCC phase I-II trial: Alternating radiotherapy and chemotherapy plus cetuximab in advanced head and neck cancer (HNC)
Authors: Merlano M. C. , Numico G. , Colantonio I. , Garrone O. , Gasco M. , Russi E. , Vigna Taglianti R. , Granetto C. , Di Costanzo G. 
Published: March 2020

15515 Background: Pfister (ASCO 2003) added Cetuximab (C) to CT/RT to evaluate toxicity and activity of this combination in advanced HNC. The trial was early stopped due to an excess of toxicity including on treatment deaths. However, the treated pts achieved an excellent long term. Results: 76% of them were alive and disease free at 24 months. Therefore, a new, less toxic scheduling of CT/RT and C is highly attractive. Alternating CT/RT (ACR) may be less toxic than concurrent CT/RT (Haffty 2000; Merlano 2003). Therefore we designed a phase I-II trial, scheduling finding, combining ACR and C. Methods: The ACR regimen consists of cisplatin 20 mg/m2 and 5FU 200 mg/m2 days 1 to 5, weeks 1, 4 and 7; and RT, 2 Gy/day, days 1 to 5, weeks 2–3, 5–6, 8–10 to a total dose of 66 Gy. ACR remains unchanged during both phase I and phase II part of the study, whereas C is given to the first 6 pts (phase I, step I) weekly only in the weeks when RT is delivered. If no limiting toxicity is observed, C is combined also with CT, in a second group of six pts (phase I step II). If again no limiting toxicity is recorded, the trial will be continued as a phase II study (optimal two-stage design, 21+24 pts, Simon 1989). Results: At the time of the present report, the phase I step I is completed and 3 pts in phase I step II are on-going. All the pts had HNC stage IVa (8 pts) or stage III (1 pt). Two pts had disease recurrence after prior surgery, while the others had previously untreated cancers. All the tumors over-expressed EGFr (+++), but the percentage of cells expressing EGFr ranges between 10 to 100% (median 70%), One episode of neutropenic fever occurred in one pt enrolled in phase I step II. All the pts developed chemoradiation expected toxicities, including stomatitis and dysphagia requiring TPN. The only unexpected toxicity was a moist desquamation occurring within the irradiated field which was observed in all but one pts at a cumulative RT dose of 50–66 Gy. This toxicity did not interfere with ACR treatment but C was stopped until recovery. Recovery occurred in 5–7 days. Four pts out of the 6 evaluable for response, reached a complete response; the two remaining achieved a PR. One of them underwent surgical removal of a residual nodal mass without complications. Conclusions: The update of the AlteRCC trial will be presented. [Table: see text]
The cytotoxicity of combined paricalcitol, docetaxel and radiation in head and neck squamous cell carcinoma
Authors: Huang T. W. , Northrup S. 
Published: March 2020

15526 Background: Paricalcitol is a calcitriol analog used in the treatment of secondary hyperparathyroidism. It produces less hypercalcemia compared to calcitriol and has low clinical toxicity. We have shown previously that paricalcitol is antiproliferative in head and neck squamous cell carcinomas (HNSCC) in vitro. However, its interaction in combination with docetaxel and radiation has not been elucidated. The purpose of this study is to evaluate the combined effects of paricalcitol, docetaxel, and radiation in vitro in SCC-15 cells, a human tongue squamous cell carcinoma cell line. Methods: The cytotoxic effects were assessed using MTT assays. SCC 15 cells were plated, allowed to attach for 24 hours, and then treated with paricalcitol at 0, 12.5, 25, or 50 nM. After 24 hours, docetaxel at 0, 0.05, 0.15, or 0.3 nM was applied, followed in 24 hours by single treatment with radiation at 0, 2, 4, or 6 Gy. MTT assays were performed after incubation for 5 days. CalcuSyn analysis was used to determine if the interaction between paricalcitol, docetaxel, and radiation is synergistic, additive, or antagonistic. Results: Paricalcitol alone at 12.5, 24, and 50 nM produced growth inhibition of 30, 38, and 40%, respectively. Docetaxel alone at 0.05, 0.15, and 0.3 nM resulted in 33, 61, and 72% growth inhibition, respectively. Radiation at 2, 4, and 6 Gy produced 44, 57, and 62% inhibition, respectively. Sequential paricalcitol and docetaxel at the concentrations tested followed by 2 Gy radiation produced additive to synergistic cytotoxicity. Antagonism was seen with 4 Gy and all combinations of paricalcitol and docetaxel. Antagonism was also seen with 6 Gy and 0.15 or 0.3 nM of docetaxel. Conclusions: Sequential application of paricalcitol, docetaxel, and then radiation at moderate doses produced additive to synergistic cytotoxicity in SCC-15 cells. The results of this study provide support for further investigations of combined paricalcitol, docetaxel and radiation therapy in the treatment of head and neck cancers. [Table: see text]
Weekly methotrexate in squamous cell cancers of head and neck
Authors: Pathak A. B. , Kulkarni H. 
Published: March 2020

15539 Background: The aim was to evaluate response rates and toxicity of weekly methotrexate in locally advanced or recurrent squamous cell cancers of the head and neck region. Methotrexate, oldest non-platinum drugs active in squamous cell cancer of head and neck, was selected for its cost-effectiveness and ease of administration. Methods: Patients with locally advanced, inoperable or recurrent squamous cancers were selected. Sites included anterior two-third tongue, buccal mucosa, alveolus, base tongue, larynx and maxilla. Methotrexate 1 mg/Kg was given intramuscularly on outpatient basis once a week for 6 to 8 weeks along with hydration. Patients who responded well and became resectable were encouraged to undergo surgery. All patients were followed up in the clinic every monthly. Results: Total 19 patients were entered on the study over a duration of 24 months. 12 out of 19 patients had partial response (63%), 5 had stable disease (26%) and 2 patients had disease progression. Symptomatic relief ranged from 25% to 100%. Maximum response duration was 12 weeks. Treatment naïve patients had rapid response. In 5 patients disease became clearly resectable. Toxicity was grade II-III oral mucositis in patients with previous radiation. Sample size is small for a subset analysis. Conclusions: Weekly methotrexate is a simple, cost-effective regimen for palliation in advanced recurrent squamous cell cancers of head and neck region. It should also be evaluated further in large scale trials and especially in neo-adjuvant setting in locally advanced squamous cell cancers of the head and neck region given its rapidity of response and brief duration of therapy. No significant financial relationships to disclose.
Induction chemotherapy with gemcitabine and cisplatin in paranasal sinus tumours
Authors: Hussain R. , Jamshed A. , Bilal M. , Shehzad K. , Azhar R. , Shah M. A. , Hameed S. , Arif M. , Faruqui Z. 
Published: March 2020

15542 Background: There is no standard treatment for locally advanced carcinoma of paranasal sinuses. Induction chemotherapy is frequently used to down stage the disease. Surgery, radiotherapy and chemoradiation are all in use to treat the primary following neoadjuvant chemotherapy treatment. Cisplatin and gemcitabine are active agents in head and neck cancers. We evaluated the response of induction chemotherapy with cisplatin and gemcitabine in carcinoma of the paranasal sinuses. Methods: Between August 2005–November 2005, 5 patients with locally advanced carcinoma paranasal sinuses received induction chemotherapy at Shaukat Khanum Cancer Hospital and Research Centre. There were three males and two females, 19 to 65 (median 45) years of age. Three patients had maxillary and 2 patients had ethmoid sinus tumors. Four patients had Stage IVa and 1 patient had Stage IVb disease. All patients had biopsy proven carcinoma. Histologically the tumour was adenocarcinoma in 1 patient and squamous cell carcinoma in 4 patients. Four patients received 2 cycles and 1 patient received 1 cycle of cisplatin 75 mg/m2 day 1 and gemcitabine 1000 mg/m2 day 1 and 8 (repeat day 22) before radical treatment. Response was assessed in all patients with pre and post induction chemotherapy with CT or MRI scan. Results: Overall response rate was 60%. Complete response was seen in one patient and over 50% tumor regression in 2 patients. Disease remained unchanged (no response) in 1 patient. One patient progressed following one cycle and did not receive the second cycle of chemotherapy treatment. The treatment was well tolerated and no grade III or IV toxicity was seen. Conclusions: The combination of gemcitabine and cisplatin in this schedule has low toxicity and significant activity in patients with locally advanced paranasal sinus tumors and is worthy of further study. No significant financial relationships to disclose.
High dose rate brachytherapy with surface applicators: Treatment for nonmelanomatous skin cancer
Authors: Musmacher J. , Ghaly M. , Satchwill K. 
Published: March 2020

15543 Background: To assess the use of HDR surface applicators as an alternative radiotherapy modality to external radiation (electrons or low-energy x-rays) for the treatment of skin lesions of the head and neck. Skin carcinomas require efficient and accurate delivery of HDR Brachytherapy, which can be precisely reproduced on an outpatient basis. Methods: Patients were treated to various sites, which included lesions of the face and scalp. Thermoplastic casts were fitted with Leipzig Surface Applicators and custom molded to the patient to treat squamous or basal cell carcinomas ≤ 2 cm in diameter. A custom surface mold applicator (Freiburg Flap) was used for lesions up to 4 cm. Planning target volume included the tumor plus a 5 mm margin. Biweekly photographs of the treatment volume were taken for documentation and monitoring of radiation reactions. Treatment was delivered by HDR Brachytherapy (Ir-192), 5 Gy per fraction, twice per week for four weeks to a 5 mm depth. TLD’s were placed at the center of the treated volume under the applicator and at critical structures (i.e. lateral canthus of the ipsilateral eye, auditory canal or gingivolabial sulcus) twice during the course of treatment. Results: Patients’ setup and reproducibility were accurate and treatment time was short which added great convenience for the patients. With the HDR surface applicators, dose distribution was uniform in the surface of the skin and at 5 mm depth in the whole area of the applicator. Differences between the areas of maximum and minimum dose at this depth did not reach values higher than 5% of the prescribed dose. At the edges of the applicators, the dose gradient was sharp, with the detected dose at 5 mm from the applicator being negligible. An exudative radiation reaction was noted in some patients, which reversed with appropriate therapy. Conclusion: High Dose Rate Brachytherapy offers a highly effective treatment of skin carcinomas. Surface applicators, used in conjunction with HDR brachytherapy equipment, make a uniform dose distribution and sharp dose gradient at the edge of the treatment field. Surface applicators are easy and safe to use, and they fit very accurately for each fraction. These applicators have the ability to become the standard treatment for skin carcinomas in the near future. No significant financial relationships to disclose.
A phase I trial of intratumoral (i.t.) administration of reovirus in patients with histologically confirmed recurrent malignant gliomas (MGs)
Authors: Forsyth P. A. , Roldan G. , George D. , Wallace C. , Morris D. G. , Cairncross J. , Vallee Matthews M. , Coffey M. , Thompson B. , Hamilton M. 
Published: March 2020

1563 Background: Reovirus is an oncolytic virus which replicates preferentially in transformed cells possessing activated Ras signaling pathways. Promising activity was found in in vivo models of MGs and in a phase I trial in patients (pts.) with cutaneous metastases from systemic cancer. We performed this dose-escalation trial of i.t. administration of reovirus to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) in pts. with recurrent MG. Response, survival and time to progression (TTP) were secondary aims. Methods: Pts. were ≥ 18 yrs old, had a KPS ≥ 60, received prior radiotherapy ± chemotherapy, a histologically proven recurrence of MG and recurred ≤ 3 times. Reovirus was administered i.t. stereotactically at one of three dose levels (1 × 107, 1 × 108 or 1 × 109 TCID50) in a volume of 0.9 mls. Results: Twelve pts. were treated at 3 dose levels; seven were men, the median (mdn) KPS was 80, mdn age was 53.5 yrs, 10 had glioblastoma multiforme, one anaplastic astrocytoma and another anaplastic oligoastrocytoma. There were the 1st, 2nd or 3rd recurrences in 6, 5 and 1 pts., respectively. During i.t. viral administration all pts. were treated with prophylactic anticonvulsants and 6 (50%) were receiving corticosteroids. The 1st, 2nd and 3rd cohorts contained 3, 6 and 3 pts., respectively. There were no grade 3 or 4 adverse events definitely or probably related to the administration of reovirus. A transient increase in GGT was possibly related to reovirus administration and a patient experienced grade 3 motor weakness that could be related to post-injection edema. Viral shedding and systemic immune responses were examined but results are pending. There were no CR, or PR; a pt. had SD, 10 PD and one was not evaluable. The mdn survival was 20 weeks (range, 6–171), 6 pts. survived > 6 months and 3 are alive 6, 7 and 40 months from the reovirus injection. The mdn TTP was 4.3 weeks (range: 3.4–39). Conclusions: A MTD was not reached. The intratumoral administration or reovirus was well tolerated in patients with recurrent MGs. Phase 2 studies in MGs are planned. [Table: see text]