7216 Background: Thatcher (JCO 2000; 18:395-404) showed that dose dense ACE with GCSF allows delivery of "chemotherapy planned dose on time" (CPDOT) leading to improved survival in subjects with extensive SCLC. The aim of this study was to show that pegfilgrastim can also support ACE 14 CPDOT in this setting.
METHODS: All 30 subjects received ACE (doxorubicin 40 mg/m(2) and cyclophosphamide 1000 mg/m(2) iv d1, etoposide 120 mg/m(2) iv d1 and 240 mg/m(2)PO d2-3) every 14 days for up to 6 cycles, with a single dose per cycle of pegfilgrastim 6 mg SC on d4. A cycle was considered "on time" if it started no more than 17 days after the start of the previous cycle, and "at planned dose" if ≥75% of drug was administered for each agent. For any given cycle, subjects were defined as having CPDOT if both criteria were satisfied.
RESULTS: 27 subjects received pegfilgrastim and at least 1 cycle of ACE and 17 received all 6 cycles of ACE. Twenty subjects (74%) had no bone marrow involvement at baseline. The mean baseline ANC was 7.4x10(9)/L (range 3.0-23.3); over the study, mean ANC levels at the start of each cycle were ≥1.5x10(9)/L and were comparable to baseline levels. All 22 subjects who started cycle 2 received full CPDOT. Of the 121 cycles delivered over the study, 107 (88%) were full CPDOT. In addition, 18 subjects (67%) received all their cycles according to full CPDOT. Of the 22 subjects who were assessed for disease response, 2 (9%) had CR, 15 (68%) PR (with ORR 77%) and 2 (9%) SD. Safety data were consistent with the underlying patient group. Nine (33%) and 6 (22%) subjects experienced hematological and non-hematological events of toxicity grade 3-4: anemia 15%, leukopenia 7%, thrombocytopenia 11%, and febrile neutropenia 15%. All other adverse events were single episodes.
CONCLUSIONS: These results indicate that pegfilgrastim enables delivery of dose intensified ACE chemotherapy every 14 days in SCLC patients. [Table: see text].
CONCLUSION: As shown by the significant influence of metastatic sites, some P die from their advanced systemic disease situation before they would experience cerebral progression, in part explaining the influence of systemic treatment. In other individuals however, intensified local treatment and systemic treatment appear to influence both cTTP and OS significantly, implicating a direct influence of systemic therapy on BM. This might result from an impaired blood brain barrier around metastatic sites, making sufficient tissue concentrations of cytotoxic agents possible. No significant financial relationships to disclose.
TREATMENT: Rx 375 mg/m(2) IV at day 1; concomitant therapy: Rasburicase, steroids only for anaphylaxis, intrathecal (IT) triple drug at days 1, 3 for CNS pts only. Begin of chemotherapy at day 5. Response evaluation: product of 2 perpendicular diameters of 1 - 3 index lesions/% blasts in BM/PB within 24 h prior to Rx and at day 5: responder (RP): at least 1 lesion with at least objective effect (decrease of ≥25%) and no progress (increase of ≥25 %) at other sites. Study plan: Simon 2-stage phase II with α and β = 5%. Response rate (RR) for poor activity was set to 45%, for good activity 65%. 33 pts entered the first stage, final evaluation after 79 pts.
METHOD: Patterns of skeletal (123)I mIBG uptake were assignednumerical scores (Mscore) ranging from 0 (no metastasis) to 72 (diffuse metastases) within 12 body areas as described previously (J Nucl Med 2009;50:1379). 271 anonymised, paired image data sets acquired at diagnosis and on completion of Rapid COJEC induction chemotherapy were reviewed, constituting a representative sample of 1602 children treated prospectively within the HR-NBL1/SIOPEN trial. Pre-and post-treatment Mscores were compared with bone marrow cytology (BM) and 3 year event free survival (EFS).
THERAPY: The indirect cost savings in terms of the value of patient time are substantial. Other potential cost factors, including hospital use, ambulatory encounters, and other medications, did not differ significantly between the regimens. If this trial meets its primary endpoint of equivalence in disease-free survival, X is likely to be cost-effective from a societal perspective compared with the Mayo Clinic regimen in the adjuvant treatment of Dukes' C colon cancer. [Table: see text].
EXCLUSIONS: brain metastases; prior chemotherapy. Pre-randomization strata: Liver metastases (Y/N); other visceral metastases or elevated serum LDH (Y/N); PS (0 vs. 1-2). Pts received DTIC 1,000 mg/m(2) Q3 weeks. Patients randomized to GNS received 7 mg/kg/d for 5 days by continuous IV infusion prior to DTIC. Primary endpoint: overall survival (OS). Secondary endpoints: progression-free survival (PFS); response rate (RR, RECIST criteria).