S. Takemoto
P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
Type: Poster
Track: Treatment of Advanced Diseases - NSCLC
Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
P1.01-045 - Drug Fever After Cancer Chemotherapy Is Most Commonly Observed on Post-Treatment Days 3-4 (ID 466)
09:30 - 17:00 | Author(s): S. Takemoto
Fever during cancer chemotherapy is require attention using antibiotics to prevention severe infection. On the other hand, it should be avoid using antibiotics to non-infectious fever such as drug and tumor fever with the object of development of resistant bacteria, exacerbation of drug fever, and medical economics.
Retrospectively, 1,016 consecutive cycles of cancer chemotherapy were analyzed. Fever was defined as a temperature of ≥37.5°C. Age, sex, tumor histology, the treatment regimen, the timing of fever onset, the number of days for which the fever persisted, the cause of the fever, and the presence or absence of radiotherapy were examined.
Seventy-four percent of the patients (748 of 1016) were males, the patients' median age was 68 years (range: from 29 to 88 years), and lung cancer was the most common disease (93%). Fevers occurred in 36% of cycles (367 of 1016) including 37% of those involving males and 32% of those involving females. There was no difference in the frequency of fever among the sexes (p=0.146). The incidence of fever according to age were 33% (≤60), 41% (61-65), 36% (66-70), 33% (71-75), 41% (76-80), and 33% (≥81); it did not differ significantly with age (p=0.424). In incidence of fever according to the drugs administered, gemcitabine was the drug that was most frequently associated with fever (41%; 43/106), followed by irinotecan (40%; 108/272), amrubicin (39%; 29/75), and docetaxel (36%; 47/131). Post-treatment days 4 (8.3%), 3 (6.8%), and 12 (6.7%) were the days on which fever was most common. The distribution of fever exhibited a bimodal distribution; i.e., whilst it peaked on post-treatment days 3 and 4; otherwise, it generally gradually increased until day 12 and then gradually decreased. The peak on post-treatment days 3-4 was considered to be due to adverse drug reactions, and the latter peak was considered to represent neutropenic or infection-based fevers. Fevers occurred on post-treatment days 3-4 in 11% of all cycles (113 of 1016) including 11% (84 of 748) of the cycles involving males and 11% (29 of 268) of those involving females. The incidence of fever on post-treatment days 3-4 according to age were 12% (≤60), 13% (61-65), 10% (66-70), 8% (71-75), 13% (76-80), and 10% (≥81); however, this parameter did not differ significantly with age (p=0.427). The incidence of fever on post-treatment days 3-4, gemcitabine was the drug that was most commonly associated with fever (20%), followed by docetaxel (18%), nedaplatin (12%), and carboplatin (11%). The patients' fevers were caused by infections (47%), adverse drug reactions (24%), unknown causes (19%), and tumors (7%). The causative infections included febrile neutropenia (50%), pneumonia (18%), unidentified infections (9%), and colitis (7%). The incidence of fever was significantly higher among the patients treated with radiotherapy than among those that did not receive radiotherapy (46% vs. 34%, p=0.001).
The febrile episodes that occurred on post-treatment days 3-4 were considered to represent adverse drug reactions after cancer chemotherapy. Physicians should be aware of this feature of chemotherapy-associated fever and avoid unnecessary examination and treatments including prescribing antibiotics.
P3.01-069 - Phase II Trial of Paclitaxel, Irinotecan, and Bevacizumab for Patients with Untreated NSCLC Overexpressed ERCC1 MRNA; Evaluated by EBUS-GS (ID 1362)
We prospectively evaluated the efficacy and toxicity of non-platinum triplet regimen, which consist of paclitaxel, irinotecan, and bevacizumab for patients with advanced non-small cell lung cancer (NSCLC) expected to be platinum resistant.
All patients were diagnosed with NSCLC using endobronchial ultrasonography with a guide sheath (EBUS-GS) system. We defined the EBUS-GS as a core biopsy. RNA was immediately isolated from this unfixed biopsy specimens, and quantitative real-time reverse transcriptase PCR assays were performed to determine the excision repair cross-complementing 1 (ERCC1) mRNA expression. Patients with advanced, untreated NSCLC showing high ERCC1 levels (ΔCt≧6.5) were entered the phase II trial of the non-platinum triplet regimen. Paclitaxel of 180mg/m2 on day 1, irinotecan of 50mg/m2 on day 1 and 8, and bevacizumab of 15mg/kg on day 1 were administered every 4 weeks. Primary end point was the objective response rate (ORR), assuming 30% for a standard therapy and 60% for a target therapy (alpha=0.05 and beta=0.1), and the estimated required total number of patients was 28 by Simon's Optimal Two-stage Design.
Total 141 untreated patients received EBUS-GS and were evaluated the expression of ERCC1, and 30 patients were entered in this trial. The ORR was 66.7%(95% confidence interval [CI]: 47.2-82.7). Median progression-free survival was 174 days. Grade 4 thrombosis occurred one patient, but other toxicities were mild and controllable. Fifty-three patients were treated with platinum-containing regimens and 22 patients were responded (ORR was 41.5% [95% CI: 28.1-55.9]). Twenty-three of these patients were high ERCC1 levels and 6 patients were responded, and 30 patients were low ERCC1 levels and 16 patients were responded (p=0.0053, by Fisher's exact test).
The triplet combination of paclitaxel, irinotecan and bevacizumab might be effective for patients with advanced, untreated NSCLC overexpressing ERCC1. ERCC1 mRNA levels extracted from unfixed lung biopsy specimens obtained by EBUS-GS also might be a predictive factor for platinum-containing regimens.