A phase Ib study of oxaliplatin in combination with fluorouracil (5FU) and leucovorin (LV) in pediatric patients (pts) with advanced solid tumors
Bibliographic record
Abstract
9548 Background: Platinums have significant activity in a wide variety of pediatric tumors, and oxaliplatin exhibits synergy with 5FU and LV in adults with colorectal cancer in FOLFOX regimens. The primary objectives of this study are to determine the maximum tolerated dose (MTD) of the modified FOLFOX6 regimen in pediatric tumors. Secondary objectives include safety, PK pharmacokinetic (PK) and PET scan efficacy analyses. Methods: Pts age <21 years with advanced cancers and adequate organ function are eligible. Patients are stratified by tumor type (CNS or non-CNS) to better delineate the potential neurotoxicity in patients with altered neurologic function. Pts received oxaliplatin starting at 85 mg/m2 and LV 400 mg/m2 over 2 hours on day 1 followed by a 5FU bolus of 400 mg/m2 then 2,400 mg/m2 continuous infusion over 46 hours, every 2 weeks (3 courses = 1 cycle), with integrated PK sampling in a limited dose escalation design. Standard 3+3 dose escalation, definitions of dose limiting toxicity (DLT), and dose modification for toxicity are implemented. The MTD is expanded to 15 patients to confirm and further characterize tolerability and toxicity. Results: To date, 15 very heavily pre-treated patients (7 M, 8 F) have received 25 cycles (range 1–4, median 2) of treatment at 2 dose levels. One of 8 pts at dose level 2 (oxaliplatin 100 mg/m2) developed DLT (delay in repeat treatment > 14 days due to grade 3 platelets). Treatment has been well tolerated. The most frequently reported related grade 3–4 adverse events (AEs) are reversible leukocytes (29%), neutropenia (43%), platelets (35%) and lymphopenia (21%). 31 of 90 courses (34%) have been delayed for neutropenia and thrombocytopenia. Anti-tumor activity to date includes a confirmed partial response lasting 15 weeks in a patient with osteosarcoma, and prolonged stable disease in 5 other pts with brain tumors (2), hepatoblastoma (2) and sarcoma (1). Conclusions: The modified FOLFOX6 regimen has significant but reversible myelosuppression in heavily pre-treated pediatric patients, but is tolerable and has promising activity in several tumor types. Cohort expansion continues at 100 mg/m2 of oxaliplatin. PET scan and pharmacokinetic analyses will be presented. No significant financial relationships to disclose.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".