Trial reportGynecologic oncology2011
Phase II trial of lapatinib and topotecan (LapTop) in patients with platinum-refractory/resistant ovarian and primary peritoneal carcinoma.
Trial report in Gynecologic oncology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Epidermal growth factor receptor blockers for the treatment of ovarian cancer.The Cochrane database of systematic reviews · 2018Pooled it
- Combined inhibition of HER2 and VEGFR synergistically improves therapeutic efficacy via PI3K-AKT pathway in advanced ovarian cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Characterization of global research trends and prospects on platinum-resistant ovarian cancer: a bibliometric analysis.Frontiers in oncology · 2023Review
- Advances in the Application of Radionuclide-Labeled HER2 Affibody for the Diagnosis and Treatment of Ovarian Cancer.Frontiers in oncology · 2022Review
- A Novel, Personalized Drug-Screening System for Platinum-Resistant Ovarian Cancer Patients: A Preliminary Clinical Report.Cancer management and research · 2021Article
- Targeted therapies in gynecological cancers: a comprehensive review of clinical evidence.Signal transduction and targeted therapy · 2020Review
- Overcoming Multidrug Resistance: Flavonoid and Terpenoid Nitrogen-Containing Derivatives as ABC Transporter Modulators.Molecules (Basel, Switzerland) · 2020Review
- Kinase Inhibitors and Ovarian Cancer.Cancers · 2019Review
- Hypoxic Microenvironment and Metastatic Bone Disease.International journal of molecular sciences · 2018Review
- Human epidermal growth factor receptor targeted inhibitors for the treatment of ovarian cancer.Cancer biology & medicine · 2018Article
- Reverse Translational Research of ABCG2 (BCRP) in Human Disease and Drug Response.Clinical pharmacology and therapeutics · 2018Review
- SYD985, a novel duocarmycin-based HER2-targeting antibody-drug conjugate, shows promising antitumor activity in epithelial ovarian carcinoma with HER2/Neu expression.Gynecologic oncology · 2017Article
- Novel ABCG2 Antagonists Reverse Topotecan-Mediated Chemotherapeutic Resistance in Ovarian Carcinoma Xenografts.Molecular cancer therapeutics · 2016Article
- Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs.International journal of oncology · 2016Article
- ABCG2 inhibition as a therapeutic approach for overcoming multidrug resistance in cancer.Journal of biosciences · 2016Review
- A Combination of Two Receptor Tyrosine Kinase Inhibitors, Canertinib and PHA665752 Compromises Ovarian Cancer Cell Growth in 3D Cell Models.Oncology and therapy · 2016Article
- Photochemical activation of MH3-B1/rGel: a HER2-targeted treatment approach for ovarian cancer.Oncotarget · 2015Article
- Analysis of wntless (WLS) expression in gastric, ovarian, and breast cancers reveals a strong association with HER2 overexpression.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2015Article
- ABC-Transporter Expression Does Not Correlate with Response to Irinotecan in Patients with Metastatic Colorectal Cancer.Journal of Cancer · 2015Article
- Comprehensive profiling of EGFR/HER receptors for personalized treatment of gynecologic cancers.Molecular diagnosis & therapy · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveResistance to chemotherapy is a major challenge in the treatment of ovarian/peritoneal cancer. One purported mechanism of topotecan resistance is the breast cancer resistance protein (BCRP) and P-glycoprotein (Pgp). We designed a phase II clinical trial evaluating the efficacy and adverse event profile of concomitant topotecan and lapatinib, a small molecule pan-erbB inhibitor that can block BCRP/Pgp efflux of topotecan.
methodsPatients with platinum-refractory or resistant epithelial ovarian/peritoneal cancer were treated with topotecan 3.2 mg/m² IV on Day 1, 8 and 15 and lapatinib 1250 mg PO daily, continuously in 28 day cycles. The primary endpoint was response rate. For correlative studies, archived tissue was assessed for expression of EGFR, HER2, HIF-1α, CD31, and BCRP.
resultsEighteen patients were enrolled and treated. Four experienced evidence of clinical benefit: one partial response and three with stable disease. Using a two-stage Simon design, the trial was stopped after the first stage due to insufficient activity. Grades 3+ and 4+ adverse events (AE) were experienced in 14 and 4 patients, respectively. The most common grade 3/4 AE were neutropenia (56%), thrombocytopenia (28%), and diarrhea (22%).
conclusionsThe combination of lapatinib plus topotecan for the treatment of platinum refractory/resistant epithelial ovarian cancer lacks sufficient activity to warrant further investigation. In particular, hematologic adverse events were substantial. Expression of correlative study markers did not reveal patterns of predicted benefit or toxicity. Disruption of erbB signaling and BCRP/Pgp efflux with lapatinib was insufficient for overcoming topotecan resistance, suggesting alternative mechanisms of resistance are involved.
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What OpenQuestion holds
Registered trials
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.