Effects of ATP infusion on glucose turnover and gluconeogenesis in patients with advanced non-small-cell lung cancer

2000 ◽  
Vol 98 (6) ◽  
pp. 689-695 ◽  
Author(s):  
H. J. AGTERESCH ◽  
S. LEIJ-HALFWERK ◽  
J. W. O. VAN DEN BERG ◽  
C. H. HORDIJK-LUIJK ◽  
J. H. P. WILSON ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Healthy Subjects ◽  
Low Dose ◽  
Small Cell ◽  
Glucose Turnover ◽  
High Dose ◽  
Small Cell Lung ◽  
Gluconeogenesis From Alanine ◽  
Nsclc Patients

Cancer cachexia is associated with elevated lipolysis, proteolysis and gluconeogenesis. ATP infusion has been found to significantly inhibit loss of body weight, fat mass and fat-free mass in patients with advanced lung cancer. The present study was aimed at exploring the effects of ATP on whole-body glucose turnover, alanine turnover and gluconeogenesis from alanine. Twelve patients with advanced non-small-cell lung cancer (NSCLC) were studied 1 week before and during 22–24 h of continuous ATP infusion. After an overnight fast, turnover rates of glucose and alanine, and gluconeogenesis from alanine, were determined using primed constant infusions of [6,6-2H2]glucose and [3-13C]alanine. Thirteen NSCLC patients and eleven healthy subjects were studied as control groups without ATP infusion. During high-dose ATP infusion (75 µg·min-1·kg-1), glucose turnover was 0.62±0.07 mmol·h-1·kg-1, compared with 0.44±0.13 mmol·h-1·kg-1 at baseline (P = 0.04). For gluconeogenesis a similar, but non-significant, trend was observed [baseline, 0.30±0.16 mmol·h-1·kg-1; during ATP, 0.37±0.13 mmol·h-1·kg-1 (P = 0.08)]. At lower ATP doses (37–50 µg·min-1·kg-1) these effects were not detected. The relative increase in glucose turnover during ATP infusion compared with baseline showed a significant correlation with the ATP dose (r = 0.58, P = 0.02). No change in alanine turnover was observed at any ATP dose. The results of this study indicate an increase in glucose turnover during high-dose ATP infusion compared with baseline levels. During high-dose ATP infusion, glucose turnover was similar to that during low-dose ATP infusion and to that in control NSCLC patients. Between ATP infusions, however, glucose turnover in patients treated with high-dose ATP was significantly lower than that in the low-dose and control NSCLC patients (P = 0.04 and P = 0.03 respectively), and similar to that in healthy subjects. This would suggest that repeated high-dose ATP infusions may inhibit glucose turnover between infusion periods.

Daily low-dose cisplatin plus concurrent high-dose thoracic irradiation in locally advanced unresectable non-small-cell lung cancer: results of a phase II Southwest Oncology Group study.

1994 ◽  
Vol 12 (9) ◽  
pp. 1814-1820 ◽  
Author(s):  
M B Hazuka ◽  
J J Crowley ◽  
P A Bunn ◽  
M O'Rourke ◽  
T J Braun ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Low Dose ◽  
Locally Advanced ◽  
Small Cell ◽  
Survival Duration ◽  
High Dose ◽  
Small Cell Lung ◽  
Stage Iiia ◽  
Thoracic Irradiation

PURPOSE This single-arm phase II trial was designed to evaluate the efficacy and toxicity of continuous-course, high-dose thoracic irradiation (RT) combined with concurrent daily low-dose cisplatin followed by high-dose cisplatin consolidation in patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). The daily chemotherapy regimen was designed to optimize the radiosensitizing properties of cisplatin. PATIENTS AND METHODS Sixty-five patients from 21 participating institutions were entered onto the study between April 1989 and May 1991. Protocol therapy consisted of daily intravenous (i.v.) cisplatin (5 mg/m2) plus concurrent continuous-course RT (61 Gy over 6 1/2 weeks) both delivered Monday through Friday each week. After a 3- to 4-week rest period, this was followed by three 28-day cycles of cisplatin at 100 mg/m2 or subsequently 50 mg/m2 administered i.v. on days 1 and 8 of each cycle. RESULTS Sixty-four patients were eligible; the majority had unresectable stage IIIa (36%) or IIIb (55%) NSCLC. The remaining 9% had recurrent disease confined to the chest (five patients) or stage II disease (one patient). The feasibility of this regimen is demonstrated by the fact that only five patients (8%) were unable to complete daily cisplatin and RT because of toxicity. Esophagitis (16%), leukopenia (14%), nausea (8%), and vomiting (6%) were the most common severe (grade 3) toxicities. There was only one life-threatening toxicity (grade 4 nausea) and no treatment-related deaths. The objective response rate was 39%, and six patients (9%) achieved a radiographic complete response (CR). The median survival duration for all patients was 14 months, and the 1- and 2-year actuarial survival rates were 56% and 24%, respectively. For stage IIIa patients, the median survival duration and 2-year survival rate were 17 months and 38%, as compared with 10 months and 14% for stage IIIb patients, respectively. CONCLUSION Daily low-dose cisplatin plus concurrent high-dose continuous-course RT is a well-tolerated out-patient regimen. The survival results are encouraging and appear to be equivalent to more toxic combined approaches. These results warrant further testing of combined daily platinum analogs with RT.

A retrospective study of low-dose apatinib combined with S-1 in patients with advanced non-small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20666-e20666
Author(s):  
Tong Zhou ◽  
Xiaoyue Zhou ◽  
Peng Li ◽  
Changling Wu ◽  
Changsong Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Retrospective Study ◽  
Small Cell Lung Cancer ◽  
Low Dose ◽  
Standard Treatment ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e20666 Background: Currently regimen for advanced non-small cell lung cancer (NSCLC) failing from standard treatment is deficient. This retrospective study aimed to assess the efficacy and safety of low-dose apatinib in combination with S-1 therapy in this NSCLC setting. Methods: In this retrospective study, advanced NSCLC patients who failed from standard treatment in Changzhou Cancer Hospital of Soochow University were screened for eligibility. Progression-free survival (PFS) was set as the primary endpoint. Overall response rate (ORR), disease control rate (DCR), Overall survival (OS) and safety profile were considered to be the secondary endpoints. Results: 31 eligible patients were included in this study. The median PFS (mPFS) was 102 days (95% CI: 57-147). 7 patients (23%; 95% CI: 11-38%) achieved an objective response and the DCR was maintained in 23 patients (75%; 95% CI: 58-86%). The median OS (mOS) was 422 days (95% CI: 148-696).Patients with smoking had a tendency for shorter overall survival without significant differences (HR = 4.105, 95% CI: 0.874-19.288, P = 0.074). Treatment-related grade 3 toxicity was observed in five patients (16%) and the common grade 1 or 2 adverse events were fatigue (42%), hypertension (32%), and hand-foot-skin reaction (23%). Conclusions: Combination of low-dose apatinib and S-1 could be effective and tolerable for advanced NSCLC patients failed from standard treatment, but further exploration in larger clinical trials is needed.

EGFR tyrosine kinase inhibitor therapy continuation with high-dose hypofractionated radiotherapy in EGFR-mutated non-small cell lung cancer (NSCLC) patients with oligoprogressive disease.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21580-e21580
Author(s):  
Mariacarmela Santarpia ◽  
Maria Rosaria Valerio ◽  
Nicolò Borsellino ◽  
Andrea Girlando ◽  
Gianfranco Mancuso ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Acquired Resistance ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
First Line ◽  
Egfr Mutant ◽  
Nsclc Patients

e21580 Background: EGFR tyrosine kinase inhibitors (TKIs) represent the standard first-line therapy for advanced non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. However, despite initial marked responses, tumors invariably develop acquired resistance to TKIs. Oligoprogression is commonly observed during treatment with oncogene-directed therapies, including EGFR TKIs, and refers to patients who experience disease progression only in limited sites as a result of heterogeneous mechanisms of resistance. The use of local ablative treatments for these resistant lesions may extend the duration of TKI therapy and potentially improve long-term disease control and survival. We e retrospectively analyzed the efficacy of EGFR TKI therapy continuation with high-dose hypofractionated radiation therapy (RT), in EGFR-mutant NSCLC patients with oligoprogressive disease. Methods: Patients with metastatic EGFR mutant NSCLC who developed oligoprogression during first-line treatment with gefitinib were included in this analysis. We evaluated progression-free survival 1 (PFS 1), defined as the time from initiation of TKI therapy until development of oligoprogression or death, and PFS 2, defined as time of focal progression until further progression of disease or death. Overall survival and safety were also assessed. Results: Thirty-six patients were included in the study. The median PFS 1 was 12.5 (4.0-23.2) months. High-dose hypofractionated RT consisted of intensity-modulated RT in 23 patients (64%) and stereotactic radiotherapy in 13 cases (36%). The median PFS 2 was 6.3 (2-12.5) months. Overall survival was 38.7 months (9.0-46.3). The treatment was well-tolerated and no patient had to discontinue TKI therapy because of adverse events during radiotherapy. Conclusions: Our therapeutic strategy, including high-dose hypofractionated RT in addition to TKI therapy, was feasible in the clinical setting and was associated with significant prolongation of disease control and improvement of survival outcomes, while being associated with manageable side effects. Our study further support the use of definitive therapeutic approaches in oligoprogressive disease, especially in oncogene-driven tumors. Molecular profiling of metastatic sites remains crucial to identify novel biomarkers, involved in the development of acquired resistance and oligoprogression, that may be useful to select patients for local treatments.

Concurrent high-dose radiotherapy with low-dose chemotherapy in patients with non-small cell lung cancer of the superior sulcus

2011 ◽  
Vol 101 (2) ◽  
pp. 278-283 ◽  
Author(s):  
Ingrid Kappers ◽  
Houke M. Klomp ◽  
Mia G.J. Koolen ◽  
Lon J. Uitterhoeve ◽  
Jaap J. Kloek ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Low Dose ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
Superior Sulcus ◽  
Low Dose Chemotherapy

Randomized study of high-dose versus low-dose methotrexate in the treatment of extensive small cell lung cancer

1982 ◽  
Vol 73 (3) ◽  
pp. 413-419 ◽  
Author(s):  
Kenneth R. Hande ◽  
Robert K. Oldham ◽  
Mehmet F. Fer ◽  
Ronald L. Richardson ◽  
F. Anthony Greco
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Low Dose ◽  
Randomized Study ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
Dose Methotrexate

P-229 Phase II evaluation of low dose suramin as a modulator of paclitaxel/carboplatin (P/C) in non-small cell lung cancer (NSCLC) patients

Lung Cancer ◽  
2003 ◽  
Vol 41 ◽  
pp. S149 ◽  
Author(s):  
Miguel A. Villalona-Calero ◽  
G. Otterson ◽  
G. Wientjes ◽  
A. Murgo ◽  
R. Jensen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Low Dose ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients
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