Example orders for CVD, IL-2, IFN alfa-2b - sequential biochemotherapy in melanoma

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019	Phase 3 (C)	1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab	Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.

Biomarker eligibility criteria

• CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

• Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
• Paclitaxel (Taxol) 175 or 200 mg/m² IV once on day 1

21-day cycle for 3 cycles

Subsequent treatment

• Complete resection

References

1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article contains dosing details in manuscript PubMed NCT02998528

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Remember that example order sets that may contain additional information about supportive medications, suggestions for monitoring, hydration, and pre-treatment screening information for chemotherapy regimens are purely anecdotal, provided only as examples of what some other providers may be using, and are typically not based on references in the primary literature.

CVD, IL-2, IFN alfa-2b - sequential biochemotherapy

CVD: Cisplatin, Vinblastine, Dacarbazine
Original references may be found at CVD, IL-2, IFN alfa-2b - sequential biochemotherapy

Example regimen #1

• Cisplatin (Platinol) 20 mg/m² IV in 250 mL NS over 30 minutes on days 1 to 4, given first
• Vinblastine (Velban) 1.2 mg/m² IV push on days 1 to 4, given second
  • Give via IV push immediately after cisplatin.
• Dacarbazine (DTIC) 800 mg/m² IV in 250 mL D5W over 1 hour on day 1, given third
• IL-2 - Aldesleukin (Proleukin) 9,000,000 units/m2/day IV continuous infusion over 96 hours on days 1 to 4
  • Continuous Infusion. Infuse each dose over 24 hours. Total of 4 doses. Mix in 250 mL D5W with 0.1% albumin. Begin at 3PM on day 1. Hold dose if bicarbonate of <18 and call house officer.
• Interferon alfa-2b (Intron-A) 5,000,000 units/m² SC on days 1 to 5, 8, 10, 12; days 8, 10, 12 given as outpatient doses
  • Give at start of Aldesleukin each day and at the completion of Aldesleukin on Day 5. To be given on days 8, 10, 12 as an outpatient.

21-day cycles x up to 4 cycles

Supportive medications

• Pegfilgrastim (Neulasta) 6 mg SC on day 6
• All antihypertensive therapy discontinued at least 24 hours before each cycle
• Naproxen 375 mg PO Q12H
• Acetaminophen 975 mg PO/PR Q6H, to begin prior to IL-2. Total acetaminophen dosage not to exceed 3900 mg/day
• Ranitidine (Zantac) 150 mg PO BID
• Cephalexin (Keflex) 500 mg PO BID on days 1 to 15
• Diphenhydramine (Benadryl) 25-50 mg PO/IV Q6H prn pruritis
• Prochlorperazine (Compazine) 10 mg PO/IV Q6H prn nausea
• Diphenoxylate-Atropine (Lomotil) 1 tab PO prn each loose stool, maximum of 8 tabs per day
• Lorazepam (Ativan) 1-2 mg PO/IV Q6H prn nausea, vomiting, anxiety, insomnnia
• Potassium chloride PO/IV sliding scale repletion; for K 3.8-3.6: 40 mEq; for K 3.5-3.3: 60 mEq; for K 3.2-3.0: 80 mEq; for K <3.0: contact NP/MD
• Calcium gluconate IV sliding scale repletion; for corrected Ca 7.5-7.1: 2 g IV; for corrected Ca <7: 3 g and contact NP/MD
• Magnesium sulfate IV sliding scale repletion; for Mg 1.6-2: 2 g IV; for Mg 1.2-1.5: 2-4 g IV; for Mg <1.2: 4 g IV and call NP/MD
• Potassium phosphate 15 mmol in 250 mL NS IV over 5 hours prn serum phosphate 1.5-2.3; if serum phosphate <1.5, call NP/MD
• Furosemide (Lasix) 20 mg IV prn urine output <100 ml/H for at least 3 hours before cisplatin is due. Call NP/MD before administering
• Meperidine (Demerol) 25-50 mg in 50 mL D5W IV over 15 minutes Q2H prn severe chills/rigors. May repeat x2; then call NP/MD
• Ondansetron (Zofran) 24 mg IV daily, 30 minutes before cisplatin on days 1 to 4
• Ondansetron (Zofran) 24 mg IV daily prn nausea/vomiting on days 5-7
• Dopamine 4 mcg/kg/min IV drip, titrate to keep SBP at least 80, prn hypotension refractory to fluid boluses. Cardiac monitor while on medication.
• Phenylephrine 1 mcg/kg/min IV drip, titrate to keep SBP at least 80, prn if target SBP not met while patient is on on maximum dopamine dose. Cardiac monitor while on medication.
• In case of anaphylaxis:
  • Methylprednisolone (Solu-Medrol) 125 mg IV x1 prn anaphylaxis
  • Diphenhydramine (Benadryl) 50 mg IV push prn anaphylaxis
  • Famotidine (Pepcid) 20 mg IV over 15 minutes
  • Epinephrine (EpiPen) 0.3 mg IM x1 prn anaphylaxis

Hydration:

• Standing IV fluids: 1 liter D5 1/2 NS with 20 mEq potassium chloride, continuous at 100 mL/H on days 1 to 4. Hold during cisplatin hydration (see below).
• For hypotension: 250 ml NS bolus over 15 minutes prn SBP <90, may repeat X1 (total 2 boluses). This order to be discontinued for weight gain >5% of baseline.
• Sodium bicarbonate-containing fluids to be used as follows:
  • If serum bicarbonate is 18-19, change IV fluids to 1 liter D5 1/2 NS with 50 mEq sodium bicarbonate, continuous at 75 mL/H. Once bicarbonate is at least 20, resume standing IV fluids above.
  • If serum bicarbonate is 16-17, administer 100 mL D5W with 100 mEq sodium bicarbonate over 1 hour and hold IL-2.
  • If bicarbonate is <16, give 100 mEq sodium bicarbonate as above and contact NP/MD
• If urine output <500 mL in an 8-hour period, give 500 mL NS bolus over 30 minutes. If urine output <250 mL over next 4 hours, call NP/MD.
• If urine output <100 mL/H for at least 3 hours before cisplatin is due, give 1000 mL NS over 1 hr prior to proceeding with cisplatin. Call NP/MD prior to administration.
• If creatinine >1.6, give 500 mL NS bolus over 60 minutes. Recheck creatinine 4 hours later, and if still >1.6, hold that day's dose of chemotherapy & call NP/MD.

Monitoring:

• As an inpatient, check daily CBC with differential, comprehensive metabolic panel including sodium, potassium, chloride, bicarbonate, BUN, creatinine, glucose, calcium, magnesium, phosphate, alkaline phosphatase, AST, ALT, total bilirubin; once every 2 day monitoring of PT/PTT

Clinical scenario & comments:

• 47 year-old gentleman with initially stage IIIC (T4b N1b M0) and now metastatic melanoma, s/p wide local excision, lymph node dissection, adjuvant interferon alfa-2B, with metastatic recurrence. At the time of treatment with this regimen, ipilimumab (which he later received) was not yet available outside of a clinical trial.