bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase II trial of single agent erlotinib vs. standard chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) and performance status (PS) of 2
Authors: Lilenbaum R. , Axerold R. , Thomas S. , Dowlati A. , Seigel L. , Albert D. , Van Duym C. , Bodkin D. 
Published: March 2020

7022 Background: A previous CALGB trial suggested a benefit for carboplatin-paclitaxel (CP) over P alone in pts with PS 2. Erlotinib (E) has activity in previously treated pts with low PS but has not been formally tested in 1st line. Methods: In a multi-center randomized phase II trial, untreated pts with advanced NSCLC and PS 2 were randomized to E 150 mg daily or CP (AUC 6 and 200 mg/m2) for 4 cycles. Pts in CP who progressed, did not tolerate, or refused further therapy were allowed to cross over to E. The primary endpoint was progression-free survival (PFS). QoL analysis was performed in all pts and tumor samples were obtained whenever possible. Results: As of 12/05, 98 of 102 projected pts have been accrued. Results are reported for 88 (46 E; 42 CP). Demographics were balanced except for more females in E (59%) than CP (45%). Most pts had stage IV adenoca histology. Never-smokers comprised 13% and 7% of pts respectively. Response for E: 2% PR and 30% SD; for CP, 10% PR and 45% SD. Gr 2–4 toxicities for E: rash (34%) and diarrhea (11%); for CP: nausea (12%), neuropathy (14%) and fatigue (29%). Median PFS was 2.5 mo for E (95%CI 1.28 - 2.79) and 4.0 mo for CP (95%CI 2.66 - 4.86). Of 42 pts in CP, 21 have crossed over to E. Conclusions: This is the first randomized phase II trial of E in PS 2 patients. Based on preliminary results, PS 2 patients seemed to fare better with standard CP than single agent E as initial therapy. Mature survival and QoL data will be available in June. [Table: see text]
Phase III study of cisplatin (P) plus etoposide (E) with concurrent chest radiation (XRT) followed by docetaxel (D) vs. observation in patients (pts) with stage III non-small cell lung cancer (NSCLC): An interim toxicity analysis of consolidation therapy
Authors: Bedano P. M. , Neubauer M. , Ansari R. , Govindan R. , Einhorn L. H. , Bruetman D. , White A. , Breen T. , Juliar B. , Hanna N. 
Published: March 2020

7043 Background: Concurrent chemo radiotherapy is the standard treatment for pts with unresectable stage III NSCLC. A previously reported phase II study (Gandara et al J Clin Oncol 2003) suggests that consolidation D after concurrent PE/XRT may further improve survival. HOG LUN01–24, is an ongoing phase III clinical trial comparing chemo radiation. A preliminary analysis of the differences in toxicities between PE/XRT with or without consolidation D was performed. Methods: Eligible pts had previously untreated, unresectable stage III NSCLC, ECOG PS 0–1 at time of study entry (and PS 0–2 at the time of randomization), ≤ 5% weight loss in preceding 3 months, FEV-1 > 1 L. Treatment consisted of P 50 mg/m2 days 1, 8, 29, 36 with E 50 mg/m2 days 1–5 and 29–33, given concurrently with chest XRT to 5,940 cGy (180 cGy/day) beginning on day 1. Non-progressive pts were randomized (4–8 weeks after completing PE/XRT) to receive D 75 mg/m2 iv every 21 days for 3 cycles vs. observation. We report an interim toxicity analysis associated to consolidation D. Results: From 3/02 to 12/05 220 have been registered and 149 pts have been randomized to consolidation D (n=73) or observation (n=76). Median age was 63.6 years (range 33–86); male/female 34.1%/65.9%; PS 0/1 at study entry 59.1%/40.9%; stage III A/B 40.6%/59.4%; 50.2% had FEV-1 > 2 (range 1–4.2); 44.3% were current smokers. Randomized pts have PS 0/1/2 44.3%/53%/2.7. Selected grade 3/4 toxicities associated to D include: neutropenia 23.3%, febrile neutropenia 8.2%, and pulmonary toxicity 9.6%. In addition, 26.7% of pts had dose modifications or delays on D arm, 45.2% had at least one grade 3/4 toxicity and 20.5% were hospitalized due to D-related toxicity, including 4 pts (5.5%) whose death was considered therapy related. Conclusions: Concurrent PE/XRT followed by consolidation D is associated with a high rate of grade 3/4 toxicities and hospitalizations, including treatment-related deaths. Updated toxicity data will be presented at the ASCO meeting. Whether consolidation D confers a survival advantage is not yet known. [Table: see text]
Three-dimensional conformal involved-field radiotherapy for stage III non-small cell lung cancer
Authors: Yuan S. , Yu J. , Sun X. , Li M. 
Published: March 2020

7044 Background: Radiation dose escalation is limited by the high incidence of pulmonary and esophageal toxicity, leading to calls for the omission of elective nodal irradiation (ENI) and the willingness to use involved-field radiotherapy (IFRT) in patients with stage III non-small cell lung cancer (NSCLC). Methods and Materials: Patients with inoperable stage III NSCLC were enrolled and patients with previous treatment were ineligible, as were those with supraclavicular nodal metastases, pleural effusion, the Karnofsky performance status of <80 or a weight loss exceeding 10% of baseline in the preceding 3 months. Two-hundred patients were treated with concurrent chemo-radiotherapy and randomized into IFRT group or ENI group. Two cycles of cisplatin-based chemotherapy (CHT) were delivered before radiotherapy, and another 2–3 cycles were followed after radiotherapy by the same or changed regime according to different response to the first 2 cycles of CHT. Radiotherapy was delivered using 3D treatment planning in once-daily fractions of 2 Gy to 68–74 Gy for IFRT or 60–64 Gy for ENI. The involved field consisted of the pre-CHT (or greatest) tumor volume, and any mediastinal nodes confirmed by biopsy or with a short-axis diameter of ≥1 cm on CT. Results: 193 patients had complete follow-up data. Radiation pneumonitis rate of patients with ENI was higher than patients with IFRT (29% vs. 17%, P = 0.044 ).The main cause of failure was local failure in 49% patients with ENI group and 41% with IFRT within 2 years. Only 7% of patients with IFRT developed a failure in an elective nodal region. Patients in IFRT group achieved a better overall response than ENI group (90% vs. 79%, P = 0.032). The overall survival at 1, 2, and 3 years was 59.7%, 25.6%, and 19.2% for ENI group vs. 67.2%, 38.7, and 27.3%for IFRT (P = 0.048). Conclusions: Local and distant failures remain the overwhelming modes of failure for stage III NSCLC patients. The omission of ENI did not result in any increase in isolated nodal failures, and it allowed a dose of 68–74 Gy to be safely administered to a substantial proportion of patients with inoperable Stage III NSCLC. Dose-escalation by conformal IFRT combined with CHT may improve the outcome for stage III NSCLC. No significant financial relationships to disclose.
Class III beta tubulin expression and benefit from adjuvant cisplatin/vinorelbine chemotherapy in operable non-small cell lung cancer: Analysis of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) study JBR.10
Authors: Reiman T. , Lai R. , Ding K. , Winton T. , Butts C. , Mackey J. , Dabbagh L. , Seymour L. , Tsao M. , Shepherd F. , Seve P. 
Published: March 2020

7051 Background: Biomarkers may be useful to select patients who will benefit from a particular chemotherapy regimen. High class III beta tubulin (bTubIII) expression in advanced NSCLC is known to correlate with reduced response rates and inferior survival with the anti-microtubule agents vinorelbine or paclitaxel. JBR.10 demonstrated a 12% and 15% improvement in 5-year recurrence-free (RFS) and overall survival (OS) respectively with the addition of cisplatin and vinorelbine following resection of stage IB-II NSCLC. We sought to determine the impact of bTubIII on patient outcome and benefit from adjuvant chemotherapy in the JBR.10 trial. Methods: We performed an immunohistochemical assay for bTubIII on primary tumor tissue available from 265 of the 482 patients in JBR.10. A validated, numerical bTubIII score was assigned by two observers based on the intensity and frequency of tumour cell staining. Tumours were classified as bTubIII “low” or “high” based on the median score. We examined the prognostic impact of bTubIII in patients treated with or without chemotherapy, and the survival benefit from chemotherapy in low versus high bTubIII subgroups. Results: High bTubIII expression was associated with poorer RFS (HR = 1.9, p = 0.01) in patients treated with surgery alone, but not in patients treated with adjuvant chemotherapy (HR = 1.1, p = .75). In the low bTubIII subgroup, the improvement in RFS with chemotherapy was non-significant (HR = 0.78, p = 0.4), while the improvement in RFS with chemotherapy was significant in the high bTubIII subgroup (HR = 0.45, p = 0.002). With Cox regression, the interaction between bTubIII status and chemotherapy treatment in predicting RFS did not reach statistical significance (p = 0.15). Results for OS were similar. Conclusions: Chemotherapy appeared to overcome the negative prognostic impact of high bTubIII expression. Greater benefit from adjuvant chemotherapy was seen in patients with high bTubIII expression. This is contrary to what has been seen in the setting of advanced disease; possible reasons for this difference are being explored. No significant financial relationships to disclose.
A prospective randomized phase III, double-blind, placebo-controlled study of thalidomide in extended-disease (ED) SCLC patients after response to chemotherapy (CT): An intergroup study FNCLCC Cleo04 - IFCT 00–01
Authors: Pujol J. L. , Breton J. L. , Gervais R. , Tanguy M. , Quoix E. , David P. , Janicot H. , Depierre A. , Gameroff S. , Maraninchi D. 
Published: March 2020

7057 Background: This study aimed at determining whether or not thalidomide prolongs survival of patients (pts) suffering from SCLC. Methods: Eligibility consisted of previously untreated ED-SCLC, age <70 years, PS ≤2, weight loss <10% and, for women, post-menopausal status. Pts were registered in the study and received two courses of PCDE given 4 weeks apart with G-CSF primary prophylaxis recommended. Afterwards, pts who experienced a response were randomized to receive four additional cycles of PCDE plus thalidomide, (400 mg daily) or placebo. The planned accrual was 200 randomised pts in order to detect a 20% survival improvement. Results: The study was shortened with final analysis performed taking into account 119 registered pts (low accrual). There were 4 toxic-deaths (3.3%). Tumour assessment performed after the first two CT courses demonstrated 11 complete responders and 86 partial responders (81.4% overall response rate). Among these pts, 92 were randomly assigned, 49 in the thalidomide group and 43 in placebo group. The 5 remaining pts were not randomised due to poor recovery from previous CT. Pre-study pts’ characteristics did not differ between the two groups. The planned six cycles of PCDE were delivered to an equal proportion of pts in both groups (75.5% versus 74.4%). Mean ± SD exposure duration to thalidomide was 4.5 months ± 2.7 and to placebo 5.1 ± 2.4 (NS). Reasons for withdrawal differed between the two groups with toxicity as main reason for thalidomide (55.3% versus 35%) and disease progression as main reason for placebo (43% versus 62%; p = 0.06). In Cox model of overall survival within the 9 months following randomisation, pts allocated to the thalidomide group had the longest survival (HR of death for pts in the thalidomide group: 0.48 [95% CI: 0.24–0.93]; p = 0.03; median survival from randomisation: 11.7 versus 8.7 months for thalidomide and placebo groups respectively); Conclusion: Thalidomide prolongs survival of pts with SCLC after response to CT. This study is a clue in favour of angiogenesis process as therapeutic window in SCLC therapy. Supported by the French League against Cancer. No significant financial relationships to disclose.
Randomized phase III study of carboplatin and paclitaxel versus vincristine, doxorubicin and cyclophosphamide chemotherapy in intermediate and poor prognosis small cell lung cancer: Preliminary results
Authors: Baka S. , Mullamitha S. , Ashcroft L. , Nagel S. , Board R. , Lorigan P. 
Published: March 2020

7059 Background: The combination of paclitaxel and carboplatin has been found to be effective in lung cancer and well tolerated. Method: This is a phase III randomized trial of paclitaxel and carboplatin (PC) versus vincristine, doxorubicin and cyclophosphamide (CAV) chemotherapy in limited or extensive stage disease patients but with a prognostic score in the intermediate or poor prognosis range.The aim of the study is to determine the one year survival rate, the objective response rate and toxicity. Patients were randomized to: four cycles of PC (paclitaxel 200mg/m2 by IV 3 hour infusion), followed by carboplatin (AUC of 6) by IV injection, 3-weekly or four cycles of CAV (cyclophosphamide 750mg/ m2, doxorubicin 40mg/ m2, vincristine 1.3mg/ m2 by IV injection) every 3-weeks. Thoracic radiotherapy was considered for appropriate patients. Results: 219 patients (110 for CAV and 109 for PC) patients were randomized. Pre-treatment characteristics were well balanced for stage, performance status, and age. There was significantly more grade 3/4 neutropenia in the CAV arm than the PC arm, 67% vs 38% (p < 0.005), whereas the PC arm, had more grade 3/4 thrombocytopenia (19% versus 8% p = 0.012). The PC arm had more grade 2 and 3 neuropathy. 56% grade 3 and 4 infections were observed on CAV arm and 35% on the PC arm (p < 0.005). Hospitalization required for severe neutropenia and infections was less with PC, compared to CAV (146 days for IV antibiotics compared to 308 days for CAV, p < 0.005). Response rates for CAV and PC were 59% and 61% respectively. One-year survival rates for the CAV arm was 6% and 13% for the PC arm. The intention to treat analysis concluded that there is statistical difference on the overall survival time in favor of PC (P = 0.014). Median survival was 94 days (CAV) and 154 (PC). Conclusions: CAV chemotherapy in SCLC patients is associated with higher risk of neutropenic sepsis than taxane based PC chemotherapy with no significant difference on the response rate. The overall survival was better for the PC arm. Final results will follow. No significant financial relationships to disclose.
A randomized double-blind phase IIa dose-finding study of ZD6474 in Japanese patients with NSCLC
Authors: Nakagawa K. , Kiura K. , Shinkai T. , Eguchi K. , Ohe Y. , Yamamoto N. , Tsuboi M. , Yokota S. , Fukuoka M. , Jiang H. 
Published: March 2020

7067 Background: ZD6474 is a once-daily oral therapy that selectively inhibits key signaling pathways in cancer by targeting vascular endothelial growth factor receptor (VEGFR)-dependent tumor angiogenesis, and epidermal growth factor receptor (EGFR)- and RET-dependent cancer cell proliferation and survival. ZD6474 was evaluated as monotherapy in an ongoing randomized, double-blind, parallel-group, Phase IIa, dose-finding, multicenter study in Japan. Methods: Patients with locally advanced or metastatic (stage IIIB/IV) or recurrent non-small-cell lung cancer (NSCLC), after failure of one or two platinum-based chemotherapy regimens, were eligible for this study. Patients were randomized to receive ZD6474 100, 200 or 300 mg/day in a 1:1:1 ratio, with stratification according to sex, histology (adenocarcinoma vs other histology) and smoking status (smoker vs non-smoker). Tumor response was assessed every 4 weeks for the first 24 weeks of treatment and then every 8 weeks until progressive disease (PD) or withdrawal due to any reasons other than PD. The primary objective was the objective response rate, as evaluated by RECIST. Secondary objectives included disease control rate, tolerability and safety. Adverse events (AEs) were assessed using CTC version 3.0. Results: A total of 53 patients (34 males/19 females, median age 60 years [range 30–78], 35 adenocarcinomas and 33 smokers) with a WHO PS status of 0 (n = 20) or 1 (n = 33) were recruited from eight centers between December 2004 and September 2005. Among 53 patients, 6 partial responses (PR; 11%, 2 males/4 females, 6 adenocarcinomas, 2 smokers/4 non-smokers) have been confirmed and disease control (PR or stable disease≥ 8 weeks) has been observed in 27 patients (51%). The most common AEs were rash and diarrhea, and asymptomatic QTc prolongation was also observed. One patient died due to drug-related interstitial lung disease. Conclusions: In this ongoing trial, ZD6474 has demonstrated antitumor activity as monotherapy in patients with refractory NSCLC, with 11% experiencing a PR and 51% having disease control. The tolerability profile of ZD6474 was consistent with that seen previously. [Table: see text]
Molecular analysis of NSCLC patients with acquired resistance to gefitinib or erlotinib
Authors: Pao W. , Balak M. N. , Riely G. J. , Li A. R. , Zakowski M. F. , Ladanyi M. , Miller V. A. 
Published: March 2020

7078 Background: We previously reported that in 2 of 5 non-small cell lung cancer (NSCLC) patients with acquired resistance to the tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, tumors biopsied after disease progression contained a second site mutation (T790M) in the epidermal growth factor receptor (EGFR) kinase domain, in addition to a primary drug-sensitive mutation (exon 19 deletion (del) or exon 21 point mutation (L858R)) (Pao et al, PLoS Med ‘05). No patients had KRAS mutations, which are associated with primary resistance to these TKIs. We sought to determine the frequency of second site EGFR kinase domain and KRAS mutations in tumors from patients with acquired resistance to TKIs, administered either as monotherapy or with chemotherapy. Methods: 18 patients with NSCLC who responded to either TKI alone (n = 14) or TKI plus chemotherapy (n = 4) and then progressed were re-biopsied. Genomic DNA samples from tumors were examined for EGFR (exons 18–24) and KRAS (exon 2) mutations. Results: Sequence analysis was successfully performed on tumors from 17 patients. The T790M EGFR mutation was detected in 6 of 13 (46%, 95% CI 19–75%) on TKI monotherapy, and in 0 of 4 (0%, 95% CI 0–53%) on TKI plus chemotherapy. In one autopsy case, the T790M mutation was detected in 5 of 5 sites, which all harbored the same exon 19 del. No other EGFR or KRAS mutations were detected. Conclusions: Secondary EGFR T790M but not KRAS mutations are commonly associated with acquired resistance to TKI monotherapy. More patients are being studied, and we are trying to elucidate determinants of acquired resistance in the absence of T790M mutations. New therapies are needed to treat and/or suppress the development of acquired resistance to gefitinib or erlotinib. Support: Joan’s Legacy, DDCF, K08-CA097980, R21-CA115051. [Table: see text]
Two-drug gemcitabine-based first-line treatment of elderly patients (pts) with small cell lung cancer (SCLC): The G-STEP program
Authors: Di Maio M. , Gallo C. , Barbera S. , Ceribelli A. , Gamucci T. , Isa L. , Piazza E. , Borsellino N. , Zagonel V. , Gridelli C. 
Published: March 2020

7089 Background: Trials testing chemotherapy for elderly pts with SCLC are scanty. Gemcitabine (Gem) is active and well tolerated. The G-STEP program looked for optimal 2-drug combination of G with either vinorelbine (Vin), etoposide (Eto), cisplatin (Cis), or carboplatin (Car). Methods: Extended stage SCLC pts, aged >70 years, PS 0–2, were eligible. Dose of G was 1,000 mg/m2, dd 1&8, every 3 weeks in all the four combinations. As safety data in the elderly were already available for Gem+Vin (Vin dose 25 mg/m2, dd 1&8), a two-stage minimax flexible design was applied with response as end-point: ≥13 responses/30 pts required at 1st stage, with p0=0.40, p1=0.60, α and β=0.10. For Gem+Car, Gem+Cis, Gem+Eto a phase 1–2 Bayesian design to select optimal dose was applied (Thall & Russell, Biometrics, 1998), with 3 possible outcomes for each patient: “active” (response and no unacceptable toxicity [UT]), “inactive” (no response, no UT), or “toxic” (UT independently of response). A response rate [RR] ≥60% and a rate of UT ≤25% were acceptable. Dose levels to explore were: Car: AUC 3.5 / 4 / 4.5, d1; Cis: 50 / 60 / 70 mg/m2, d1; Eto: 60 / 70 / 80 mg/m2, dd 1,2,3. Results: From May 2000 to September 2005, 78 eligible pts were enrolled; median age was 74 years (42% of pts older than 75yrs). In the whole group, median progression-free survival and overall survival were 20.3 weeks (95% CI 17.6 - 24.1) and 33.7 weeks (95% CI 23.7 - 41.6), respectively. Study of Gem+Vin was closed for inactivity after 1st stage with 11 responses / 30 pts (RR 36.7%, 95% exact CI: 19.9–56.1). Gem+Eto arm was closed after 10 pts (5 inactive and 5 toxic) because too high probability (0.994) of inactivity. Gem+Cis arm was closed after 12 pts (2 active, 5 inactive, 5 toxic) because too high probability (0.988) of inactivity. With Gem+Car (December 2005: 2 pts ongoing, 24 analysed: 12 active, 6, inactive and 6 toxic), RR in the 20 pts receiving Car at AUC 3.5 was 60% (95% exact CI: 36.1–80.9). Conclusions: The combination of gemcitabine and carboplatin seems promising for future trials in elderly patients with extended SCLC. The G-STEP program was supported by GIOGER. No significant financial relationships to disclose.
Compliance with oral topotecan in patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC)
Authors: Eckardt J. R. , Ramlau R. , Gervais R. , Shepherd F. , O’Brien M. , Ciuleanu T. , Dharan B. , Wissel P. , Ross G. 
Published: March 2020

7092 Background: Compliance with chemotherapy can affect treatment efficacy and patient safety. Selecting an oral chemotherapy regimen with good tolerability in appropriate patients is important. To determine general level of compliance of oral topotecan, a retrospective analysis was conducted on 3 international open-label, multicenter, 2-arm randomized, phase III studies of patients with NSCLC and SCLC. Methods: Patients were randomized to receive oral topotecan d1–5 q21d as follows: Study 387 (Ramlau et al, Proc ASCO, 2005) 2.3 mg/m2/d second-line vs IV docetaxel for NSCLC; Study 389 (Eckardt et al, Proc ASCO, 2005) 1.7 mg/m2/d first-line with cisplatin vs etoposide/cisplatin for extensive-disease SCLC; and Study 478 (O’Brien et al, Lung Cancer 2005) 2.3 mg/m2/d second-line vs best supportive care for SCLC. Oral topotecan was administered to the patient in the clinic on day 1 of each course and the patient was responsible for self-administering the oral capsules the remaining 4 days of dosing. Patient compliance was defined as 100x(sum of number of caps taken across courses)/(sum of number of caps dispensed across courses), where number of caps taken = number of caps dispensed-number of caps returned. Results: Accrual per arm was (387), 414 patients; (389) 389; (478) 71. In the treated population for all three groups, adherence to oral topotecan was high, with >90% of patients recording at least 90% overall compliance (Table). Mean age (% ≥65 years/%PS 2) was (387) 58.8 years (29.2%/14%), (389) 59.7 (32.6%/13%), and (478) 59.8 (33.8%/27%). Median oral topotecan dose intensity (% target) for each course was (387) 87%, (389) 95%, and (478) 98%. The most common reason for dose reductions or delays was hematological toxicity. Conclusions: Oral topotecan can be administered on an outpatient basis with a high degree of patient compliance in the treated population, which included those ≥65 years and those with poor PS. [Table: see text] [Table: see text]