ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Phase I oncology studies: evidence that in the era of targeted therapies patients on lower doses do not fare worse.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 4 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
62 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Skipping a pillar does not make for strong foundations: Pharmacokinetic-pharmacodynamic reasoning behind the shape of dose-response relationships in oncology.CPT: pharmacometrics & systems pharmacology · 2023Pooled it
- Dosing Three-Drug Combinations That Include Targeted Anti-Cancer Agents: Analysis of 37,763 Patients.The oncologist · 2017Pooled it
- Is the "3+3" dose-escalation phase I clinical trial design suitable for therapeutic cancer vaccine development? A recommendation for alternative design.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Pooled it
- Dose-levels and first signs of efficacy in contemporary oncology phase 1 clinical trials.PloS one · 2011Pooled it
- Challenges, opportunities, and innovative statistical designs for precision oncology trials.Annals of translational medicine · 2022Trial
- Determination of a radotinib dosage regimen based on dose-response relationships for the treatment of newly diagnosed patients with chronic myeloid leukemia.Cancer medicine · 2018Trial
- Lapatinib Plasma and Tumor Concentrations and Effects on HER Receptor Phosphorylation in Tumor.PloS one · 2015Trial
- Exposure-response relationship of AMG 386 in combination with weekly paclitaxel in recurrent ovarian cancer and its implication for dose selection.Cancer chemotherapy and pharmacology · 2012Trial
- Investigation of Profile-Related Evidence Determining Individualized Cancer Therapy (I-PREDICT) N-of-1 Precision Oncology Study: Molecular Profiling to Match Individually Dosed, Personalized Drug Combinations.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Observational
- Cracking the resistance code: The molecular reclassification of cancer and precision therapy strategies.Seminars in cancer biology · 2025Review
- Prospective assessment of health-related quality of life in early phase oncology clinical trials: PEARLER.JNCI cancer spectrum · 2025Article
- Randomized optimal selection design for dose optimization.Biometrics · 2025Article
- Improving the Dosing Schedules of Targeted Anticancer Agents.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Advancing cancer drug development with mechanistic mathematical modeling: bridging the gap between theory and practice.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- Clinical outcome assessment trends in clinical trials-Contrasting oncology and non-oncology trials.Cancer medicine · 2023Article
- Dosing of 3 Targeted Agents in Novel Drug Combinations Used at the Precision Medicine Clinic of the University of California San Diego.Journal of hematology oncology pharmacy · 2023Article
- Patient-centered dosing: oncologists' perspectives about treatment-related side effects and individualized dosing for patients with metastatic breast cancer (MBC).Breast cancer research and treatment · 2022Article
- Embracing Project Optimus: Can we Leverage Evolutionary Theory to Optimize Dosing in Oncology?Pharmaceutical research · 2022Article
- Determining drug dose in the era of targeted therapies: playing it (un)safe?Blood cancer journal · 2022Review
- Healthy volunteers in first-in-human oncology drug development for small molecules.British journal of clinical pharmacology · 2022Review
2 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
purposeTo safely assess new drugs, cancer patients in initial cohorts of phase I oncology studies receive low drug doses. Doses are successively increased until the maximum tolerated dose (MTD) is determined. Because traditional chemotherapy is often more effective near the MTD, ethical concerns have been raised about administration of low drug doses to phase I patients. However, a substantial portion of oncology trials now investigate targeted agents, which may have different dose-response relationships than cytotoxic chemotherapies. EXPERIMENTAL
designTwenty-four consecutive trials treating 683 patients between October 1, 2004, and June 30, 2008, at MD Anderson Cancer Center were analyzed. Patients were assigned to a low-dose (<or=25% MTD), medium-dose (25-75% MTD), or high-dose (>or=75% MTD) group, and groups were compared for response rate, time-to-treatment failure, progression-free survival, overall survival, and toxicity. To remove negatively biasing data from the high-dose group, in a second analysis, patients treated above the MTD were excluded (high-dose group, 75-100% MTD). Of the 683 patients, 97.7% received targeted agents.
resultsEven when excluding patients above the MTD, there was an early trend favoring the low- versus high-dose group in time-to-treatment failure, with 32.9% versus 25.2% of patients on therapy at 3 months (P = 0.08). In addition, the low-dose group fared at least as well as the other groups in all other outcomes, including response rate, progression-free survival, overall survival, and toxicity.
conclusionsThese data may help alleviate concerns that patients who receive low drug doses on contemporary phase I oncology trials fare worse and suggest targeted agents may have different dose-response relationships than cytotoxic chemotherapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.