Phase II trial of docetaxel in patients with advanced cutaneous malignant melanoma previously untreated with chemotherapy.

PURPOSE A phase II study was undertaken to determine the efficacy of docetaxel in patients with metastatic malignant melanoma. PATIENTS AND METHODS Between June 1992 and March 1994, 40 patients with metastatic malignant melanoma and no prior chemotherapy were treated with docetaxel 100 mg/m2 administered intravenously over 1 hour every 21 days. None of the patients had brain metastasis. Toxicity and follow-up data are provided. RESULTS One patient had a histologically confirmed complete response that lasted for 14+ months. Four patients had partial responses, bringing the overall response rate to 12.5% (95% confidence interval [CI], 6% to 30%). A patient with a partial response had a single chest-wall metastasis and was rendered free of disease surgically after a maximal response to docetaxel and remained free of tumor recurrence after 18+ months. Tumor was stabilized in 22 patients. The overall median survival time was 13 months. The main hematologic toxicity was neutropenia, which was severe but transient. Peripheral neuropathy was the limiting nonhematologic toxicity in three patients. Other important toxicities included cutaneous toxicity, fluid retention, oral mucositis, and hypersensitivity reactions. Preadministration of dexamethasone and diphenhydramine reduced the incidence of hypersensitivity reactions, cutaneous toxicities, and fluid retention. CONCLUSION Docetaxel has definite but low-level activity against malignant melanoma. Further investigation of this drug should be conducted in multidrug combination programs.

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Phase II study of fotemustine (F), cisplatin (CDDP), and tamoxifen (TAM) in metastatic malignant melanoma (MMM)

Melanoma Research ◽

10.1097/00008390-199303000-00115 ◽

1993 ◽

Vol 3 (1) ◽

pp. 34

Author(s):

K. A. Semb ◽

S. Aamdal ◽

T. Bohmann ◽

C. Lucas ◽

B. Gerard

Keyword(s):

Malignant Melanoma ◽

Phase Ii ◽

Phase Ii Study ◽

Metastatic Malignant Melanoma

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Clinical and pharmacokinetic phase II study of fotemustine(F), cisplatin (C) and high-dose tamoxifen (T) in metastatic malignant melanoma (MMM)

Melanoma Research ◽

10.1097/00008390-199706001-00026 ◽

1997 ◽

Vol 7 (Supplement 1) ◽

pp. S8

Author(s):

K A Semb ◽

S Aamdal ◽

T Bohmann ◽

C Lucas ◽

B Gerard

Keyword(s):

Malignant Melanoma ◽

Phase Ii ◽

Phase Ii Study ◽

Metastatic Malignant Melanoma ◽

High Dose

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Phase II trial of flavopiridol, a cyclin dependent kinase inhibitor, in untreated metastatic malignant melanoma

Investigational New Drugs ◽

10.1023/b:drug.0000026258.02846.1c ◽

2004 ◽

Vol 22 (3) ◽

pp. 315-322 ◽

Cited By ~ 54

Author(s):

Susan Burdette-Radoux ◽

Richard G. Tozer ◽

Reinhard C. Lohmann ◽

Ian Quirt ◽

D. Scott Ernst ◽

...

Keyword(s):

Malignant Melanoma ◽

Phase Ii ◽

Kinase Inhibitor ◽

Phase Ii Trial ◽

Metastatic Malignant Melanoma ◽

Cyclin Dependent Kinase ◽

Cyclin Dependent Kinase Inhibitor

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Phase II Trial of Carboplatin in Patients with Metastatic Malignant Melanoma

American Journal of Clinical Oncology ◽

10.1097/00000421-199304000-00015 ◽

1993 ◽

Vol 16 (2) ◽

pp. 152-155 ◽

Cited By ~ 18

Author(s):

A. Chang ◽

M. Hunt ◽

D. R. Parkinson ◽

H. Hochster ◽

T. J. Smith

Keyword(s):

Malignant Melanoma ◽

Phase Ii ◽

Phase Ii Trial ◽

Metastatic Malignant Melanoma

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Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.1.187 ◽

1998 ◽

Vol 16 (1) ◽

pp. 187-196 ◽

Cited By ~ 296

Author(s):

R Bruno ◽

D Hille ◽

A Riva ◽

N Vivier ◽

W W ten Bokkel Huinnink ◽

...

Keyword(s):

Febrile Neutropenia ◽

Phase Ii ◽

Independent Predictor ◽

Large Population ◽

Systemic Exposure ◽

Fluid Retention ◽

Population Pharmacokinetic ◽

Hematologic Toxicity ◽

Phase Ii Studies ◽

Time To Onset

PURPOSE The population pharmacokinetic/pharmacodynamic (PK/PD) approach was prospectively integrated in the clinical development of docetaxel to assess the PK profile in a large population of patients and investigate systemic exposure as a prognostic factor for clinical outcome. PATIENTS AND METHODS PK analysis was performed at first course in 24 phase II studies of docetaxel monotherapy using four randomized limited-sampling schedules. Bayesian estimates of clearance (CL), area under the concentration-time curve (AUC), and peak and duration of plasma levels greater than threshold levels were used as measures of exposure. PD data included for efficacy, response rate, time to first response, and time to progression (TTP) in breast cancer and non-small-cell lung cancer (NSCLC), and for toxicity, grade 4 neutropenia, and febrile neutropenia at first course and time to onset of fluid retention. PK/PD analysis was conducted using logistic and Cox multivariate regression models. RESULTS PK protocol implementation was successful. Most of the patients registered (721 of 936, 77%) were sampled and 68% were assessable for PK (640 patients). First-course docetaxel AUC was a significant predictor (P = .0232) of TTP in NSCLC (n = 151). Docetaxel CL was a strong independent predictor (P < .0001) of both grade 4 neutropenia and febrile neutropenia (n = 582). Cumulative dose was the strongest predictor (P < .0001) of the time to onset of fluid retention (n = 631). However, the duration of exposure over 0.20 micromol/L (0.16 microg/mL) at first course was an independent predictor (P = .0029). Few patients (n = 25, 4%) received the recommended dexamethasone premedication. CONCLUSION First-course docetaxel PK is a predictor of first-course hematologic toxicity, but also of fluid retention, which is cumulative in nature. Patients with elevated hepatic enzymes have a 27% reduction in docetaxel CL and are at a higher risk of toxicity. A starting dose of 75 mg/m2 is currently being evaluated in this population. Prospective implementation of large-scale population PK/PD evaluation is feasible in early drug development and this approach generates clinically relevant findings.

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Etoposide and carboplatin: a highly effective combination in relapsed or refractory Wilms' tumor--a phase II study by the French Society of Pediatric Oncology.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.5.931 ◽

1994 ◽

Vol 12 (5) ◽

pp. 931-936 ◽

Cited By ~ 48

Author(s):

F Pein ◽

M F Tournade ◽

J M Zucker ◽

M Brunat-Mentigny ◽

A Deville ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Study ◽

Wilms Tumor ◽

Complete Response ◽

Hematologic Toxicity ◽

French Society ◽

Effective Combination ◽

Major Toxicity ◽

The Cost ◽

Grade Iii

PURPOSE Since we had previously demonstrated encouraging efficacy of etoposide in patients with relapsed or refractory Wilms' tumor (WT), the likely synergism between etoposide and platinum compounds prompted us to conduct a phase II study of a combination with carboplatin. PATIENTS AND METHODS Twenty-six relapsed or refractory WT patients were included in a phase II study of two courses of combination etoposide 100 mg/m2/d for 5 days and carboplatin 160 mg/m2/d for 5 days, with a 21-day interval between the two courses. Initial stages were I (n = 2), II (n = 8), III (n = 6), IV (n = 6), V (n = 3), and unknown (n = 1). Sites of diseases were lung(s) (11 patients), abdomen-pelvis or liver or primary tumor (six patients), and multiple (eight patients). Histology was unfavorable in three of 26 patients. RESULTS Complete response (CR) was documented in eight patients and partial remission (PR) in 11 (overall response rate, 73%). Stable disease (SD) was observed in five patients and progressive disease (PD) in two. Thrombocytopenia (grade IV) was the major toxicity, and platelet transfusions were required in all but two patients. Grade III anemia and grade III to IV neutropenia were seen in 19 and 23, respectively, of 25 assessable first courses. Venoocclusive disease of the liver was fatal in one child who had undergone irradiation to the whole abdomen, 8 weeks before study. CONCLUSION Combination etoposide and carboplatin has impressive activity in refractory or relapsed WT at the cost of high-grade hematologic toxicity, especially thrombocytopenia. It is of great interest in second-line therapy, since eight of 26 patients are still alive in continuous CR (median follow-up duration, 40 months; range, 24 to 56). This combination deserves further investigation as first-line or consolidation treatment.

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