What is the recommended dosing schedule for Dacarbazine (DTIC) in the treatment of melanoma, comparing 1q3w (every 3 weeks) to day 1-5 regimens?

Dacarbazine Dosing Schedule for Melanoma

For metastatic melanoma, dacarbazine should be administered as a single dose of 850-1000 mg/m² intravenously every 3 weeks (1q3w), rather than the traditional day 1-5 schedule, as this provides equivalent efficacy with improved tolerability and convenience. 1, 2

FDA-Approved Dosing Regimens

The FDA label provides two approved schedules for dacarbazine in malignant melanoma 1:

• Day 1-5 schedule: 250 mg/m² IV daily for 5 days, repeated every 3 weeks
• Day 1-10 schedule: 2-4.5 mg/kg/day IV for 10 days, repeated every 4 weeks

Evidence-Based Preferred Schedule

Single-dose dacarbazine (850-1000 mg/m² every 3 weeks) is the current standard reference therapy for advanced melanoma, despite not being explicitly listed in the original FDA approval 2. This schedule delivers the same total dose per cycle as the day 1-5 regimen but offers several advantages:

• Equivalent efficacy to multiple-dose schedules with response rates of 10-20% 3
• Better tolerability with modern antiemetics managing nausea effectively 2
• Improved patient convenience requiring fewer clinic visits 2
• Reduced healthcare resource utilization 2

Clinical Context: Dacarbazine's Current Role

Dacarbazine is no longer first-line therapy for metastatic melanoma and has been superseded by immune checkpoint inhibitors and targeted therapies 3. Current ASCO guidelines (2020,2023) recommend:

• First-line for BRAF wild-type: Ipilimumab plus nivolumab, nivolumab monotherapy, or pembrolizumab 3
• First-line for BRAF V600 mutant: Dabrafenib plus trametinib, encorafenib plus binimetinib, or vemurafenib plus cobimetinib 3, 4

Dacarbazine is listed as an option in older NCCN guidelines (2012) but without category 1 evidence, ranking below ipilimumab and vemurafenib 3.

Combination Regimens Are Not Recommended

Dacarbazine-based combination chemotherapy or biochemotherapy does not improve survival compared to dacarbazine alone and increases toxicity 3:

• CVD (cisplatin, vinblastine, dacarbazine) showed no survival benefit over dacarbazine monotherapy 3
• Dartmouth regimen (dacarbazine, carmustine, cisplatin, tamoxifen) failed to demonstrate superiority 3
• Biochemotherapy (dacarbazine plus interferon-alfa and IL-2) increased response rates but not overall survival, with substantially higher toxicity 3

Practical Administration Details

When dacarbazine is used, the 1q3w schedule should be administered as follows 1:

• Reconstitution: 200 mg vial with 19.7 mL sterile water; 500 mg vial with 49.25 mL sterile water (final concentration 10 mg/mL)
• Administration: IV infusion after further dilution in 5% dextrose or normal saline
• Storage: Reconstituted solution stable 72 hours at 4°C or 8 hours at room temperature
• Diluted solution: Stable 24 hours at 4°C or 8 hours at room temperature

Expected Outcomes with Dacarbazine

Response rates are modest with dacarbazine monotherapy 3:

• Overall response rate: 10-20%
• Median response duration: 3-4 months
• Median overall survival: 6-9 months historically

Critical Caveat

Dacarbazine should only be considered when modern immunotherapy and targeted therapy are contraindicated, unavailable, or after progression on these agents 3. The dramatic survival improvements with checkpoint inhibitors (median OS >2 years with combination ipilimumab/nivolumab) and targeted therapy make dacarbazine obsolete as first-line treatment 3, 5.