A phase I trial of high-dose palliative radiotherapy plus concurrent weekly Vinorelbine and Cisplatin in patients with locally advanced and metastatic NSCLC

Abstract

The role of concurrent chemoradiotherapy (CRT) in patients with non-small-cell lung cancer (NSCLC) unsuitable for radical therapy but who require locoregional treatment has not been defined. The aims of this phase I trial were thus to develop a novel regimen of weekly chemotherapy concurrent with high-dose palliative RT (40 Gy/20 fractions) and assess its tolerability, objective and symptomatic response rates. Eligible patients had stage I -IIIB NSCLC unsuitable for radical RT or limited stage IV disease, ECOG PSp1 and required locoregional therapy. Treatment was RT (40 Gy/20 fractions/5 per week) and weekly Vinorelbine plus Cisplatin escalated in six planned dose levels (DLs). At 4 weeks post-RT, patients received two cycles of Cisplatin 80 mg m À2 day 1 þ Vinorelbine 25 mg m À2 days 1, 8, 15. Dose-limiting toxicities (DLTs) were defined in the CRT phase. Disease-related symptoms were assessed by the Lung Cancer Symptom Scale. In all, 24 patients accrued, stage IIIB (n ¼ 12) and IV disease (n ¼ 10). The highest administered dose was at DL 4, Vinorelbine 30 mg m À2 þ Cisplatin 20 mg m À2 with DLTs of grade 4 neutropenia in two of three patients. No grade 3 or 4 nonhaematological toxicities were observed. The overall radiological response rate was 65% (n ¼ 23: complete response 4% and partial response 61%) and infield FDG-PET responses were seen in 89% (n ¼ 18). There was an improvement or stabilisation of symptoms and quality of life. Dose level 3, Vinorelbine 25 mg m À2 þ Cisplatin 20 mg m À2 , is recommended for further assessment. This regimen was tolerable and produced meaningful responses for patients for whom locoregional control is required, but who are unsuitable for radical CRT.

Effect of co-administration of Bee honey and some chemotherapeutic drugs on dissemination of hepatocellular carcinoma in rats

“…In accordance with the present study Hassanen et al [110], declared that rats injected by DEN followed by CCl 4 and treated with 1.5 mg/kg cisplatin reflected inhibition in GGT activity compared to untreated rats. On the other hand, Michael et al [111] used cisplatin in the treatment of patients bearing locally advanced and metastatic non-small-cell lung cancer (NSCLC), demonstrated significant improvement in the enzyme level compared to untreated patients.…”

Use and Reporting of Patient-Reported Outcomes in Trials of Palliative Radiotherapy

“…Among the published trials, 116 trials (52%) used PROs. PROs were primary end points in 45 trials 20,26,28,30,[34][35][36][37]42,48,53,[56][57][58][61][62][63]66,70,74,75,77,79,83,85,93,94,97,103,[108][109][110]113,115,117,118,124,125,127,128,130,133,134,137 (20% of all published trials; 31% of 145 trials clearly stating their primary end point; 39% of 116 trials including a PRO) and secondary end points in 71 trials 24,25,27,29,[31][32][33]…”

A Randomized Phase II Trial of Two Regimens of Moderate Dose Chemoradiation Therapy for Patients with Non-small Cell Lung Cancer Not Suitable for Curative Therapy: Trans Tasman Radiation Oncology Study TROG 03.07

“…Both regimens reported here are tolerable with toxicities similar to those reported in the respective phase I trials. 10,11 Arm A used a higher radiation dose and two agents as concurrent therapy, and therefore it is not unexpected that it was associated with greater toxicity relative to arm B. However, there was no difference in QOL or treatment delivery.…”

“…One involved a combination of 40 Gy in 20 fractions over 4 weeks with concurrent weekly vinorelbine and cisplatin. 10 In 24 patients enrolled, there was a radiological response rate of 65% with only mild hematological toxicity and a median progression-free survival (PFS) and overall survival (OS) of 6.1 and 13.5 months, respectively. The second involved a combination of 30 Gy in 15 fractions over 3 weeks with concurrent weekly flat dose gemcitabine.…”