| Title |
Phase I clinical and pharmacokinetic study of PM01183 (a tetrahydroisoquinoline, Lurbinectedin) in combination with gemcitabine in patients with advanced solid tumors
|
|---|---|
| Published in |
Investigational New Drugs, November 2016
|
| DOI | 10.1007/s10637-016-0410-3 |
| Pubmed ID | |
| Authors |
Luis Paz-Ares, Martin Forster, Valentina Boni, Sergio Szyldergemajn, Jesús Corral, Samantha Turnbull, Antonio Cubillo, Carlos Fernandez Teruel, Iker López Calderero, Mariano Siguero, Patrick Bohan, Emiliano Calvo |
| Abstract |
Background To determine the recommended dose (RD) of a combination of PM01183 and gemcitabine in patients with advanced solid tumors. Methods Forty-five patients received escalating doses of PM01183/gemcitabine on Days 1 and 8 every 3 weeks (d1,8 q3wk) following a standard 3 + 3 design. Results PM01183 3.5 mg flat dose (FD)/gemcitabine 1000 mg/m(2) was the highest dose level tested. Dose-limiting toxicities (DLTs) were mostly hematological and resulted in the expansion of a lower dose level (PM01183 3.5 mg FD/gemcitabine 800 mg/m(2)); 19 patients at this dose level were evaluable but >30% had DLT and >20% had febrile neutropenia. No DLT was observed in 11 patients treated at PM01183 3.0 mg FD/gemcitabine 800 mg/m(2), which was defined as the RD. This regimen was feasible and tolerable with manageable toxicity; mainly grade 3/4 myelosuppression. Non-hematological toxicity comprised fatigue, nausea, vomiting, and transaminases increases. Fifteen (33%) patients received ≥6 cycles with no cumulative hematological toxicity. Pharmacokinetic analysis showed no evidence of drug-drug interaction. Nine of 38 patients had response as per RECIST (complete [3%] and partial [21%]), for an overall response rate (ORR) of 24% (95% Confidence Interval [CI] 12-40%). Eleven patients (29%) had disease stabilization ≥4 months. Responses were durable (median of 8.5 months): overall median progression-free survival (PFS) was 4.2 months (95% CI, 2.7-6.5 months). Conclusions The RD for this combination is PM01183 3.0 mg FD (or 1.6 mg/m(2))/gemcitabine 800 mg/m(2) d1,8 q3wk. This schedule is well tolerated and has antitumor activity in several advanced solid tumor types. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 37 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 6 | 16% |
| Student > Master | 5 | 14% |
| Researcher | 4 | 11% |
| Student > Postgraduate | 3 | 8% |
| Student > Doctoral Student | 2 | 5% |
| Other | 8 | 22% |
| Unknown | 9 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 6 | 16% |
| Biochemistry, Genetics and Molecular Biology | 5 | 14% |
| Nursing and Health Professions | 5 | 14% |
| Agricultural and Biological Sciences | 3 | 8% |
| Computer Science | 3 | 8% |
| Other | 6 | 16% |
| Unknown | 9 | 24% |
Attention Score in Context
This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 November 2021.
All research outputs
#2,898,972
of 23,008,860 outputs
Outputs from Investigational New Drugs
#70
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Outputs of similar age
#58,867
of 415,879 outputs
Outputs of similar age from Investigational New Drugs
#2
of 8 outputs
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