What is the use and administration of Cisplatin (Cddp) in cancer treatment?

Cisplatin (CDDP) in Cancer Treatment: Administration and Uses

Cisplatin is a platinum-based chemotherapeutic agent widely used for treating multiple cancer types including bladder, testicular, ovarian, head and neck, lung, esophageal, and cervical cancers, with specific administration protocols required to maximize efficacy while minimizing toxicity.

Mechanism of Action

Cisplatin works by:

• Crosslinking with purine bases on DNA 1
• Interfering with DNA repair mechanisms
• Causing DNA damage that induces apoptosis in cancer cells 1, 2

Approved Cancer Indications

Cisplatin is FDA-approved for:

• Metastatic testicular tumors: 20 mg/m² IV daily for 5 days per cycle 3
• Metastatic ovarian tumors: 75-100 mg/m² IV per cycle every 4 weeks 3
• Advanced bladder cancer: 50-70 mg/m² IV per cycle every 3-4 weeks 3

Common Regimens in Clinical Practice

Bladder Cancer

• DDMVAC (dose-dense methotrexate, vinblastine, doxorubicin, cisplatin) with growth factor support 4
• Gemcitabine and cisplatin for 4 cycles 4
• CMV (cisplatin, methotrexate, vinblastine) for 3 cycles 4

Esophageal and Esophagogastric Junction Cancers

• ECF (epirubicin, cisplatin, 5-FU) as perioperative chemotherapy 4
• Cisplatin plus paclitaxel or docetaxel, with or without 5-FU 4
• Cisplatin plus 5-FU (CF) - most commonly used regimen 4

Penile Cancer

• Cisplatin in combination with 5-FU or irinotecan for T3 or N1-N2 disease 4
• Cisplatin plus gemcitabine for metastatic disease 4
• Ifosfamide, paclitaxel, and cisplatin in neoadjuvant setting 4

Cervical Cancer

• Cisplatin-based combination regimens preferred over single agents for metastatic disease 4
• Cisplatin/paclitaxel and cisplatin/topotecan show higher response rates than cisplatin alone 4

Administration Protocol

Preparation and Administration

1. Pre-hydration: 1-2 liters of fluid infused for 8-12 hours prior to cisplatin dose 3
2. Dilution: Dilute in 2 liters of 5% Dextrose in 1/2 or 1/3 normal saline containing 37.5g of mannitol 3
3. Infusion: Administer by slow IV infusion over 6-8 hours 3
4. Post-hydration: Maintain adequate hydration and urinary output for 24 hours following administration 3

Critical Administration Notes

• NEVER give by rapid intravenous injection 3
• Do not use needles or IV sets containing aluminum parts (causes precipitate formation) 3
• Do not dilute cisplatin in just 5% Dextrose Injection 3
• Protect solution from light if not used within 6 hours 3

Nephrotoxicity Prevention

Cisplatin-induced nephrotoxicity is dose-limiting and requires preventive measures:

1. Hydration protocol: Pre-hydration with isotonic saline (1-2L) prior to cisplatin and post-hydration continuing for several hours after infusion 5
2. Electrolyte supplementation: Add 8-16 mEq of magnesium to hydration regimen for nephroprotection 5
3. Monitoring: Check renal function before each cycle (BUN, creatinine, serum uric acid, creatinine clearance) 5
4. Dose adjustment: Consider dose reduction (75 mg/m² vs 100 mg/m²) to decrease toxicity 5
5. Treatment intervals: Do not administer repeat course until serum creatinine is below 1.5 mg/100 mL and/or BUN is below 25 mg/100 mL 3

Special Considerations for Different Cancer Types

Bladder Cancer

• Neoadjuvant cisplatin-based chemotherapy shows survival benefit in muscle-invasive bladder cancer 4
• DDMVAC is preferred over standard MVAC based on better tolerability and efficacy 4
• For borderline renal function, split-dose administration may be considered (35 mg/m² on days 1 and 2 or days 1 and 8) 4
• Carboplatin should NOT be substituted for cisplatin in perioperative setting 4

Hepatocellular Carcinoma

• Hepatic arterial infusion chemotherapy (HAIC) with low-dose FP (cisplatin plus 5-FU) shows efficacy for HCC with portal vein tumor thrombosis 4
• CDDP monotherapy (65 mg/m²) can be administered every 1-2 months as HAIC 4

Toxicity Management

Major Toxicities

1. Nephrotoxicity: Most significant dose-limiting toxicity
2. Myelosuppression: Monitor blood counts before repeat courses (platelets ≥100,000/mm³, WBC ≥4,000/mm³) 3
3. Ototoxicity: Perform audiometric analysis before subsequent doses 3
4. Nausea/vomiting: Requires aggressive antiemetic protocols
5. Electrolyte disturbances: Monitor magnesium, calcium, and potassium levels 5

Anaphylactic Reactions

• Can occur within minutes of administration
• Symptoms: facial edema, wheezing, tachycardia, hypotension
• Management: epinephrine, corticosteroids, antihistamines 3

Common Pitfalls and Caveats

1. Overdosage risk: Exercise extreme caution to prevent inadvertent overdosage. Doses >100 mg/m²/cycle are rarely used 3
2. Renal function: Cisplatin is contraindicated in patients with pre-existing renal impairment
3. Elderly patients: Require closer monitoring due to higher susceptibility to nephrotoxicity 5
4. Drug resistance: Many patients develop resistance, requiring consideration of alternative platinum compounds 1, 6
5. Combination therapy: Often more effective than single-agent therapy to overcome resistance and reduce toxicity 7

Alternative Platinum Compounds

For patients who cannot tolerate cisplatin or develop resistance:

• Carboplatin: Less nephrotoxic but more myelosuppressive 8
• Oxaliplatin: Alternative for certain cancers with different toxicity profile 4

Remember that cisplatin administration requires careful attention to hydration protocols, monitoring of renal function, and management of potential toxicities to maximize therapeutic benefit while minimizing adverse effects.