The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
A phase I clinical, plasma, and cellular pharmacology study of gemcitabine.
Abstract
A novel deoxycytidine analog, gemcitabine (2',2'-difluorodeoxycytidine [dFdC]), has been studied in a phase I clinical and pharmacology trial. Doses ranging from 10 to 1,000 mg/m2 were administered over 30 minutes weekly times 3 weeks every 4 weeks. The maximum-tolerated dose (MTD) was 790 mg/m2. The dose-limiting toxicity was myelosuppression, with thrombocytopenia and anemia quantitatively more important than granulocytopenia. Nonhematologic toxicity was minimal. Two responses in patients with adenocarcinomas of the colon and lung were documented. The maximum dFdC plasma concentration, reached after 15 minutes of infusion, was proportional to the total dose administered. Elimination, due mainly to deamination, was rapid (terminal half-life [t1/2], 8.0 minutes) and dose independent. The deamination product 2',2'-difluorodeoxyuridine (dFdU) was eliminated with biphasic kinetics characterized by a long terminal phase (t1/2, 14 hours); it was the sole metabolite detected in urine. The concentration of dFdC 5'-triphosphate in circulating mononuclear cells increased in proportion to the dFdC dose at infusions between 35 and 250 mg/m2. No further increment in dFdC 5'-triphosphate (dFdCTP) was observed at higher doses, which resulted in plasma dFdC concentrations greater than 20 mumol/L (350 to 1,000 mg/m2), suggesting saturation of dFdC 5'-phosphate accumulation. The recommended dose for phase II clinical trials in solid tumors is 790 mg/m2/wk.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Prediction of Creatinine Clearance from Serum Creatinine
Cockcroft, D. W., & Gault, H. (1976) · Nephron · doi:10.1159/000180580 · Cited by 15,309
Reporting results of cancer treatment
Miller, A. B., Hoogstraten, B., Staquet, M., & Winkler, A. (1981) · Cancer · doi:10.1002/1097-0142(19810101)47:1<207::aid-cncr2820470134>3.0.co;2-6 · Cited by 7,793
Evaluation of the antitumor activity of gemcitabine (2',2'-difluoro-2'-deoxycytidine).
Hertel, L. W., Boder, G. B., Kroin, J. S., Rinzel, S. M., Poore, G. A., Todd, G. C., & Grindey, G. B. (1990) · PubMed · Cited by 680
Heinemann, V., Hertel, L. W., Grindey, G. B., & Plunkett, W. K. (1988) · PubMed · Cited by 504
Levin, H. S., High, W. M., Goethe, K. E., Sisson, R. A., Overall, J. E., Rhoades, H. M., Eisenberg, H. M., Kalisky, Z., & Gary, H. E. (1987) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.50.2.183 · Cited by 484
Inhibition of ribonucleotide reduction in CCRF-CEM cells by 2',2'-difluorodeoxycytidine.
Heinemann, V, Xu, Y. Z., Chubb, S., Sen, A., Hertel, L. W., Grindey, G. B., & Plunkett, W. (1990) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09518-5 · Cited by 399
Synthesis of 2-deoxy-2,2-difluoro-D-ribose and 2-deoxy-2,2'-difluoro-D-ribofuranosyl nucleosides
Hertel, L. W., Kroin, J. S., Misner, J. W., & Tustin, J. M. (1988) · The Journal of Organic Chemistry · doi:10.1021/jo00246a002 · Cited by 366
Studies of the enzymatic deamination of cytosine arabinoside—I
Camiener, G. W., & Smith, C. G. (1965) · Biochemical Pharmacology · doi:10.1016/0006-2952(65)90175-9 · Cited by 292
Grunewald, R., Kantarjian, H. M., Keating, M., Abbruzzese, J. L., Tarassoff, P. G., & Plunkett, W. (1990) · PubMed · Cited by 209
Self-citation
Cited by
Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., et al. (2009) · Science · doi:10.1126/science.1171362 · Cited by 3,170
Overview of resistance to systemic therapy in patients with breast cancer
Gonzalez-Angulo, A. M., Morales-Vasquez, F., & Hortobagyi, G. N. (2007) · Advances in Experimental Medicine and Biology · doi:10.1007/978-0-387-74039-3_1 · Cited by 904
Dose Escalation Methods in Phase I Cancer Clinical Trials
Le Tourneau, C., Lee, J. J., & Siu, L. L. (2009) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/djp079 · Cited by 867
Cellular pharmacology of gemcitabine
Mini, E., Nobili, S., Caciagli, B., Landini, I., & Mazzei, T. (2006) · Annals of Oncology · doi:10.1093/annonc/mdj941 · Cited by 842
The mechanism of action of radiosensitization of conventional chemotherapeutic agents
Lawrence, T. S., Blackstock, A. W., & McGinn, C. (2003) · Seminars in Radiation Oncology · doi:10.1053/srao.2003.50002 · Cited by 296
Metadata
- Authors
- Abbruzzese, J. L., Grunewald, R., Weeks, E. A., Gravel, D., Adams, T., Nowak, B., Mineishi, S., Tarassoff, P., Satterlee, W., & Raber, M. N.
- Venue
- Journal of Clinical Oncology
- Published
- 1991-03
- Volume
- 9
- Issue
- 3
- Pages
- 491-498
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W1890647543
- Cited by
- 759
- References
- 9
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- closed
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. https://app.cochat.ai/papers/10.1200/jco.1991.9.3.491
- The paper
- Abbruzzese, J. L., Grunewald, R., Weeks, E. A., Gravel, D., Adams, T., Nowak, B., Mineishi, S., Tarassoff, P., Satterlee, W., & Raber, M. N. (1991). A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. Journal of Clinical Oncology. https://doi.org/10.1200/jco.1991.9.3.491
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
