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MELANOMA
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
|
Cisplatin Dacarbazine Interferon Interleukin-2 (Flaherty LE, et al. J Clin Oncol. 2001;19:3194-3202)
N = 44 |
Cisplatin 25 mg/m2/d IV 1 hour days 1-3, followed immediately by Dacarbazine 250 mg/m2/d IV over minutes days 1-3 Interferon alfa 2b 5 MU/m2/d SQ days 6, 8, 10, 13, and 15 Interleukin-2 18 MU/m2/d days 6-10 (Monday-Friday) and days 13-15 of each treatment cycle Repeat cycle every 28 days Appropriate premedications listed in Section 2, Commonly Used Premedication Regimens
|
Neutropenia* Grade III-IV 23% Leukopenia* Grade III-IV 6%
*percentage of cycles |
Grade III-IV* 2%
*Percentage of cycles |
Thrombocytopenia* 6% Anorexia* 5% Fatigue* 3% Nausea* 9% Vomiting* 9% Nephrotoxicity* 1% Transaminases* 3%
*Percentage of cycles |
Days 1-3― level 5 Days 6-10― and 13-15 ―level 4 |
No hospitalizations were required for neutropenic fever or infection dose reductions (treatment cycles 2-6) for toxicity 2 deaths possibly related to treatment Corticosteroids were omitted from this regimen, potentially accounting for the high incidence of Grade III-IV emetogenic toxicities |
|
CVD (Lagha SS, et al. Cancer. 1989;64:2024-29)
N = 50 |
Cisplatin 20 mg/m2/d IV days 2-5 Vinblastine 1.6 mg/m2/d IV days 1-5 Dacarbazine 800 mg/m2 IV day 1 Repeat cycle every 21 days |
Grade IV 50%
|
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Neutropenic Fever 30% Thrombocytopenia 26% Nausea/Vomiting* 86% Renal* 12% Diarrhea* 34% Hypomagnesemia** 68% Neuropathy† 20%
*Grade unknown **Requiring replacement †Moderately severe |
Days 1-5― level 5 |
Hospitalization 10% Treatment was discontinued in 6% of patients due to renal toxicity Dose-limiting toxicity was peripheral neuropathy |
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Dacarbazine (chapman PB, et al. J Clin Oncol. 1999;17:2745-51)
N = 121 |
Dacarbazine 1000 mg/m2 IV day 1 Repeat cycle every 21 days |
Neutropenia Grade III 10% Grade IV 9% Leukopenia with- out neutropenia Grade III 1% |
Grade III-IV 6% |
Thrombocytopenia 7% Nausea/Vomiting 5% Dyspnea 1% |
Day 1― level 5 |
3 patients removed from the study for toxicity |
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Dacarbazine (Middleton MR, et al. J Clin Oncol. 2001;18:158-66)
N = 149 |
Dacarbazine 250 mg/m2/d IV over 30 minutes days 1-5 Repeat cycle every 21 days
|
Neutropenia Grade III 1 % Grade IV 1 %
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Grade IV 1% |
Fever (Grade III) 2% Thrombocytopenia 8% Asthenia (Grade III) 1% Fatigue (Grade III) 2% Headache (Grade III) 1% Pain (Grade III) 13% Constipation (Grade III) 3% Nausea (Grade III) 4% Vomiting (Grade III) 4% Somnolence (Grade III) 1% |
Days 1-5― level 3 |
Delayed cycles 6% Discontinuation secondary to adverse events 5% Not toxic deaths Dose reductions in 2% of cycles |
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MELANOMA (continued ) : Page 2
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
|
Dacarbazine Carmustine Cisplatin Tamoxifen (Rusthoven JJ, et al. J Clin Onocl. 1996;14:2083-90)
N= 101 with tamoxifen N= 98 without tamoxifen
|
Dacarbazine 220 mg/m2/d IV days 1-3 and days 22-24 Carmustine 150 mg/m2/d IV day 1 Cisplatin 25 mg/m2/d IV days 1-3 and days 22-24 Tamoxifen 160 mg/d PO 7 days before chemotherapy, then 40 mg/d days 1-42 Repeat cycle every 21 days |
Neutropenia (without tamoxifen) Grade IV 31 % (With tamoxifen ) Grade IV 32 % |
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Neutropenic Fever 5% Infection (requiring antibiotics) 2% Deep Vein Thrombosis 6% Thrombocytopenia (Grade IV) 43% Hot Flashes without tamoxifen (Grade III) 1% with tamoxifen (Grade III) 3% Vomiting* 40%
*Grade unknown |
Days 1-3― level 5 Days 22-24 ―level 5 |
Toxic mortality 1% Hemorrohage requiring transfusion 9.5% |
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Dartmouth Regimen (chapman PB, et al. J Clin Oncol. 1999;17:2745-51)
N = 119
|
Tamoxifen 10 mg PO twice daily (start 1 week prior to chemotherapy and continue indefinitely ) Carmustine (BCNU) 150 mg/m2/d IV day 1 (repeat every 42 days- every other cycle) Cisplatin 25 mg/m2/d IV days 1-3 Dacarbazine 220 mg/m2/d IV days 1-3 Repeat cisplatin and Dacarbazine every 21 days |
Neutropenia Grade III 24 % Grade IV 15 % Leukopenia with- out neutropenia Grade III 8 % Grade IV 1% |
Grade III-IV 32% |
Thrombocytopenia 57% Nausea/Vomiting 18% Fatigue 7% Increased Serum Creatinine 3% Dyspnea 5% |
Days 1-3― level 5 |
patients removed from the study for toxicity |
|
DTIC, CDDP, Vinblastine IFN-alfa 2b, Interleukinn-2 (McDermott DF, et al. Clin Cancer Res, 2000; 2201-08 )
n = 44 |
Dacarbazine 800 mg/m2 IV day 1 Cisplatin 20 mg/m2 / d IV days 1-4 Vinblastine 1,3 mg/m2/ d / SQ days 1-5, 8, 10 , 12 Aldesleukin 9 MU/m2/ d IV continuous infusion days 1-4 Filgrastime 5 mcg/kg/d SQ days 7-16 Repeat cycle every 21 days for a maximum of 4 cycles Appropriate premedications listed in Section 2, Commonly Used Premedicaiton Regimens |
Neutropenia Grade IV 30 % |
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Neutropenic Fever 9% Infection 7% Thrombocytopenia 43% Hypotension 30% Nausea/Vomiting 27% Renal Insufficiency 11% Neurologic Toxicity 5% Bleeding 2% |
Days 1-4― level 5 Days 5, 8, 10, 12― level 1 |
34% of patients required delay in discharge or readmission for febrile neutropenia or dehy- dration secondary to nausea and vomiting Prophylactic antibiotics, antipyretics, antipruritics, and H2-blockers were used A maximum of 4 cycles were administered |
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MELANOMA (continued ) : Page 3
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
|
High –dose Interferon alfa 2b (Kirkwood JM, et al, J Clin Oncol . 2001; 19:2370-80)
N= 385 |
Interferon – alfa 2b 20 Mu/ m2 / d IV 5 days per week for 4 weeks, then 10 MU/m2/d SQ Tiw for 48 weeks |
Granulocytopenia / Leukopenia Grade III 51.3.% Grade IV 8.6 % |
|
Infection 4.3% Fatigue 20.9% Myalgia (Grade III) 3.8% Nausea (Grade III) 4.6% Vomiting 4.6% Liver 26.9% Neurosensory (Grade III) 1.8% Neuromotor (Grade III) 5.1% Neuropsychologic 9.9% Neuroclinical 16.3% Injection Site Reaction (Grade III) 0.3% |
Level 1 |
10% discontinued treatment secondary to toxicity During induction treatment, 24% had a treatment delay, 14% had a dose reduction, and 28% had a delay or reduction secondary to toxicity During maintenance treatment, 32% had a delay, 24% had a dose reduction, and 37% had a delay or reduction secondary to toxicity |
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High-Dose Aldesleukin (Atkins MB, et al. J Clin Oncol. 1999;17:2105-16)
N = 270 |
Aldesleukin 600,000 IU/kg or 720,000 IU/kg IV over 15 minutes every 8 hours days 1-5 for 14 doses; after 6- to 9-day rest period, an additional 14 doses of aldesleukin were scheduled over the next 5 days (courses were separated by 6- to 12-week intervals, with a maximum of 5 courses) Appropriate premedications listed in Section 2, Commonly Used Premedication Regimens
Note: Five patients received either 360,000 IU or 540,000 IU/kg. |
Leukopenia Grade III 1% Grade IV 1%
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Grade III-IV 2% |
Infection 11% Sepsis 2% Fever 19% Hypotension 45% Tachycardia 3% Myocardial Infarction 1% Myocardial Ischemia 2% Nausea 6% Vomiting 37% Diarrhea 32% Mucositis 2% Confusion 13% Somnolence 3% Coma 1% Increased SGOT 7% Increased Alkaline phosphatase 2% Dyspnea 10% ARDS 9% Hyperbilirubinemia 9% Oliguria 39% Increased Serum Creatinine 1% Thrombocytopenia 17% Anuria 8% Rash 2% Malaise 14% |
Days 1-5― level 3 |
6 patients died from treatment-related toxicity |
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MELANOMA (continued ) : Page 4
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
|
Temozolomide (Middleton MR, et al. J Clin Oncol. 2000;18:158-66)
N = 156 |
Temozolomide 200 mg/m2/d PO days 1-5 Repeat cycle every 28 days |
Neutropenia Grade III 1% Grade IV 2% |
Grade III-IV 2% |
Fever 2% Thrombocytopenia 7% Asthenia (Grade III) 3% Fatigue (Grade III) 3% Headache 6% Pain (Grade III) 7% Constipation (Grade III) 3% Nausea (Grade III) 4% Vomiting 5% |
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Delayed cycles 6% Discontinuation secondary to adverse events 3% 3 toxic deaths: 1 cerebral hemorrhage with thrombocytopenia 1 cerebral hemorrhage without thrombocytopenia 1 coma |