Phase II Randomized Study of Plitidepsin (Aplidin), Alone or in Association with L-carnitine, in Patients with Unresectable Advanced Renal Cell Carcinoma
Abstract
:1. Introduction
2. Results and Discussion
2.1. Patients and methods
Patient selection criteria
Study design and endpoints
Drug administration and concomitant medication
Diagnostic process
Statistics
2.2. Results
Study patients
Protocol adherence
Duration of treatment and reasons for treatment discontinuation
2.3. Progression free and response rate
2.4. Duration of response, progression-free interval and overall survival
2.5. Safety
2.6. Discussion
Acknowledgments
References and Notes
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Arm A | Arm B | Total | ||||
---|---|---|---|---|---|---|
n | % | n | % | % | ||
No. of patients | 19 | 100.0 | 20 | 100.0 | 39 | 100.0 |
Gender | ||||||
Male | 13 | 68.4 | 16 | 80.0 | 29 | 74.4 |
Female | 6 | 31.6 | 4 | 20.0 | 10 | 25.6 |
Race | ||||||
Caucasian | 19 | 100.0 | 18 | 90.0 | 37 | 94.9 |
Hispanic | . | . | 2 | 10.0 | 2 | 5.1 |
Age (years) | ||||||
Median | 56.0 | . | 56.0 | . | 56.0 | . |
Range | 28.0–75.0 | . | 42.0–74.0 | . | 28.0–75.0 | . |
ECOG PS | ||||||
0 | 10 | 52.6 | 10 | 50.0 | 20 | 51.3 |
1 | 9 | 47.4 | 10 | 50.0 | 19 | 48.7 |
Histology of primary tumor | ||||||
Chromophobic | 1 | 5.3 | . | . | 1 | 2.6 |
Clear cell carcinoma | 16 | 84.1 | 19 | 95.0 | 35 | 89.6 |
Epidermoid and clear cell carcinoma | . | . | 1 | 5.0 | 1 | 2.6 |
Mixed clear cell carcinoma | 1 | 5.3 | . | . | 1 | 2.6 |
Papillary carcinoma | 1 | 5.3 | . | 1 | 2.6 | |
No. of metastatic sites | 2 | . | 2 | . | 2 | . |
Median (range) | (1–5) | . | (1–5) | . | (1–5) | . |
Time from diagnosis to plitidepsin (months) | . | |||||
Median | 13.8 | 19.1 | . | 13.8 | . | |
Range | 1.0–109.5 | . | 1.0–109.9 | . | 1.0–109.9 | . |
Surgery | ||||||
Yes | 16 | 84.2 | 19 | 95.0 | 35 | 89.7 |
No | 3 | 15.8 | 1 | 5.0 | 4 | 10.3 |
Radiotherapy | ||||||
Yes | 4 | 21.1 | 6 | 30.0 | 10 | 25.6 |
No | 15 | 78.9 | 14 | 70.0 | 29 | 74.4 |
Immunotherapy | ||||||
Yes | 14 | 73.7 | 15 | 75.0 | 29 | 74.4 |
No | 5 | 26.3 | 5 | 25.0 | 10 | 25.6 |
Prior immunotherapy agents | 19 | 100.0 | 18 | 100.0 | 37 | 100.0 |
n | 7 | 36.8 | 11 | 61.1 | 18 | 48.6 |
Interferon | 7 | 36.9 | 4 | 22.2 | 11 | 29.8 |
Interleukin-2 | 5 | 26.3 | 3 | 16.7 | 8 | 21.6 |
Chemotherapy | ||||||
Yes | 5 | 26.3 | 6 | 30.0 | 11 | 28.2 |
No | 14 | 73.7 | 14 | 70.0 | 28 | 71.8 |
ARM A | NCI-CTC grade | |||||
---|---|---|---|---|---|---|
1 | 2 | 3 | ||||
n | % | n | % | n | % | |
Constipation | 2 | 10.5 | . | . | . | . |
Diarrhea | 5 | 26.3 | . | . | . | . |
Nausea | 10 | 52.6 | 4 | 21.1 | . | . |
Vomiting | 9 | 47.4 | 2 | 10.5 | 1 | 5.3 |
Asthenia | 4 | 21.1 | 6 | 31.6 | 3 | 15.8 |
Edema | 3 | 15.8 | . | . | . | . |
Injection site reaction | 3 | 15.8 | 2 | 10.5 | 1 | 5.3 |
Weight decreased | 2 | 10.5 | . | . | . | . |
Anorexia | 7 | 36.8 | 2 | 10.5 | . | . |
Muscle cramps | 2 | 10.5 | 1 | 5.3 | . | . |
Muscle weakness | 2 | 10.5 | 3 | 15.8 | . | . |
Myalgia | 3 | 15.8 | 3 | 15.8 | 1 | 5.3 |
Dizziness | 2 | 10.5 | . | . | . | . |
Folliculitis | 2 | 10.5 | . | . | . | . |
Rash | 1 | 5.3 | . | . | . | . |
ARM B | NCI-CTC grade | |||||
1 | 2 | 3 | ||||
n | % | n | % | n | % | |
Constipation | 2 | 10.0 | . | . | . | . |
Diarrhea | 4 | 20.0 | 3 | 15.0 | . | . |
Nausea | 7 | 35.0 | 9 | 45.0 | . | . |
Stomatitis | 2 | 10.0 | . | . | . | . |
Vomiting | 10 | 50.0 | 6 | 30.0 | . | . |
Asthenia | 2 | 10.0 | 10 | 50.0 | 1 | 5.0 |
Injection site reaction | 3 | 15.0 | 2 | 10.0 | 1 | 5.0 |
Anorexia | 6 | 30.0 | 3 | 15.0 | 1 | 5.0 |
Myalgia | 5 | 25.0 | 5 | 25.0 | 1 | 5.0 |
NCI-CTC grade | ||||||
---|---|---|---|---|---|---|
1 | 2 | 3 | ||||
n | % | n | % | n | % | |
Arm A | ||||||
Hemoglobin | 7 | 36.8 | 11 | 57.9 | 1 | 5.3 |
Lymphocytes | 2 | 10.5 | 3 | 15.8 | 3 | 15.8 |
Neutrophils | 1 | 5.3 | . | . | . | . |
Platelets | . | . | 1 | 5.3 | 1 | 5.3 |
WBC | . | . | 1 | 5.3 | . | . |
Arm B | ||||||
Hemoglobin | 12 | 60.0 | 6 | 30.0 | 1 | 5.0 |
Lymphocytes | . | . | 3 | 15.8 | 2 | 10.5 |
Neutrophils | 1 | 5.3 | . | . | . | . |
Platelets | 3 | 15.8 | . | . | 1 | 5.3 |
WBC | 2 | 10.5 | . | . | . | . |
NCI-CTC grade | ||||||||
---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | |||||
n | % | n | % | n | % | n | % | |
Arm A | ||||||||
ALT | 5 | 26.3 | 3 | 15.8 | 4 | 21.1 | . | . |
AP | 6 | 31.6 | 3 | 15.8 | . | . | . | . |
AST | 9 | 47.4 | 2 | 10.5 | 2 | 10.5 | . | . |
CPK | 3 | 15.8 | 2 | 10.5 | . | . | 1 | 5.3 |
Creatinine | 10 | 52.6 | 2 | 10.5 | . | . | . | . |
GGT | 4 | 21.1 | 4 | 21.1 | 7 | 36.8 | . | . |
LDH | 10 | 55.6 | 2 | 11.1 | . | . | 1 | 5.6 |
Total bilirubin | 3 | 15.8 | . | . | . | . | . | . |
Hypoalbuminemia | 9 | 52.9 | 4 | 23.5 | . | . | . | . |
Hypercalcemia | 7 | 36.8 | . | . | 1 | 5.3 | . | . |
Hypocalcemia | 2 | 10.5 | 6 | 31.6 | . | . | . | . |
Hyperglycemia | 11 | 57.9 | 4 | 21.1 | 2 | 10.5 | . | . |
Hypoglycemia | 1 | 5.3 | 1 | 5.3 | . | . | . | . |
Hyperkalemia | 2 | 10.5 | 3 | 15.8 | 1 | 5.3 | . | . |
Hypokalemia | 5 | 26.3 | . | . | 2 | 10.5 | . | . |
Hypernatremia | 2 | 10.5 | . | . | . | . | . | . |
Hyponatremia | 6 | 31.6 | . | . | 1 | 5.3 | 1 | 5.3 |
Arm B | ||||||||
ALT | 6 | 30.0 | 3 | 15.0 | 6 | 30.0 | . | . |
AP | 12 | 60.0 | 1 | 5.0 | . | . | . | . |
AST | 5 | 25.0 | 6 | 30.0 | 1 | 5.0 | . | . |
CPK | 5 | 25.0 | 3 | 15.0 | 1 | 5.0 | . | . |
Creatinine | 8 | 40.0 | 4 | 20.0 | 2 | 10.0 | . | . |
GGT | 5 | 25.0 | 6 | 30.0 | 4 | 20.0 | 2 | 10.0 |
LDH | 10 | 50.0 | 2 | 10.0 | . | . | . | . |
Total bilirubin | 1 | 5.0 | 1 | 5.0 | 1 | 5.0 | . | . |
Hypoalbuminemia | 6 | 31.6 | 4 | 21.1 | . | . | . | . |
Hypercalcemia | 7 | 35.0 | . | . | 1 | 5.0 | . | . |
Hypocalcemia | 6 | 30.0 | 2 | 10.0 | 1 | 5.0 | 1 | 5.0 |
Hyperglycemia | 8 | 40.0 | 5 | 25.0 | 3 | 15.0 | . | . |
Hypoglycemia | 1 | 5.0 | 2 | 10.0 | . | . | . | . |
Hyperkalemia | 4 | 20.0 | . | . | 3 | 15.0 | 1 | 5.0 |
Hypokalemia | 5 | 25.0 | . | . | 1 | 5.0 | . | . |
Hypernatremia | 2 | 10.0 | . | . | . | . | . | . |
Hyponatremia | 6 | 30.0 | . | . | 1 | 5.0 | . | . |
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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Schöffski, P.; Guillem, V.; Garcia, M.; Rivera, F.; Tabernero, J.; Cullell, M.; Lopez-Martin, J.A.; Pollard, P.; Dumez, H.; Garcia del Muro, X.; et al. Phase II Randomized Study of Plitidepsin (Aplidin), Alone or in Association with L-carnitine, in Patients with Unresectable Advanced Renal Cell Carcinoma. Mar. Drugs 2009, 7, 57-70. https://doi.org/10.3390/md7010057
Schöffski P, Guillem V, Garcia M, Rivera F, Tabernero J, Cullell M, Lopez-Martin JA, Pollard P, Dumez H, Garcia del Muro X, et al. Phase II Randomized Study of Plitidepsin (Aplidin), Alone or in Association with L-carnitine, in Patients with Unresectable Advanced Renal Cell Carcinoma. Marine Drugs. 2009; 7(1):57-70. https://doi.org/10.3390/md7010057
Chicago/Turabian StyleSchöffski, Patrick, Vincente Guillem, Margarita Garcia, Fernando Rivera, Josep Tabernero, Martin Cullell, Jose Antonio Lopez-Martin, Patricia Pollard, Herlinde Dumez, Xavier Garcia del Muro, and et al. 2009. "Phase II Randomized Study of Plitidepsin (Aplidin), Alone or in Association with L-carnitine, in Patients with Unresectable Advanced Renal Cell Carcinoma" Marine Drugs 7, no. 1: 57-70. https://doi.org/10.3390/md7010057