What it's for (Indications)
- Cisplatin, a potent platinum-based antineoplastic agent, is a cornerstone of combination chemotherapy regimens across a broad spectrum of malignant neoplasms.
- Its established primary indications include the treatment of metastatic testicular cancer, where it is often a key component of curative regimens, particularly in combination with other cytotoxic agents.
- It is also extensively utilized in the management of advanced ovarian cancer, frequently administered in conjunction with taxanes to enhance therapeutic efficacy.
- Furthermore, cisplatin plays a crucial role in treating advanced bladder cancer, encompassing both muscle-invasive and metastatic forms.
- Its efficacy extends to head and neck squamous cell carcinoma, especially in recurrent, metastatic, or locally advanced disease settings.
- Other significant indications for cisplatin therapy encompass non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), esophageal cancer, and cervical cancer.
- The broad utility of cisplatin is attributed to its potent cytotoxic activity against rapidly dividing cells, rendering it an indispensable agent in contemporary oncology practice for various solid tumors, often within multidisciplinary treatment approaches.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | Cisplatin must be administered by slow intravenous infusion. It should NOT be given by rapid intravenous injection. Needles or intravenous sets containing aluminum parts should not be used for preparation or administration as aluminum reacts with cisplatin, causing precipitate formation and loss of potency. - **Metastatic Testicular Tumors:** Usual dose is 20 mg/m² IV daily for 5 days per cycle, in combination with other approved chemotherapeutic agents. - **Metastatic Ovarian Tumors:** Usual dose is 75 to 100 mg/m² IV per cycle once every 4 weeks (Day 1) when used in combination with cyclophosphamide (cyclophosphamide dose: 600 mg/m² IV once every 4 weeks on Day 1). |
Safety & Warnings
Common Side Effects
- Nephrotoxicity (dose-related and cumulative renal insufficiency, including acute renal failure, major dose-limiting toxicity; noted in 28-36% of patients with a single dose of 50 mg/m²; manifested by elevations in BUN and creatinine, serum uric acid, and/or decrease in creatinine clearance; becomes more prolonged and severe with repeated courses; associated with renal tubular damage; elderly patients may be more susceptible).
- Ototoxicity (may be more pronounced in children).
Serious Warnings
- Black Box Warning: Cisplatin should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available. Cumulative renal toxicity associated with cisplatin is severe. Other major dose-related toxicities are myelosuppression, nausea, and vomiting. Ototoxicity, which may be more pronounced in children, can also occur.
- Administer under the supervision of a qualified physician experienced in cancer chemotherapy.
- Adequate diagnostic and treatment facilities must be readily available for managing therapy and complications.
- Cumulative renal toxicity is severe and a major dose-limiting toxicity.
- Other major dose-related toxicities include myelosuppression, nausea, and vomiting.
- Ototoxicity can occur, potentially more pronounced in children.
- Renal function must return to normal before subsequent doses.
- The administration using a 6- to 8-hour infusion with intravenous hydration and mannitol has been used to reduce nephrotoxicity, though toxicity can still occur.
How it Works (Mechanism of Action)
Cisplatin exerts its profound antineoplastic effects through a complex mechanism primarily centered on its ability to form irreversible DNA adducts, thereby disrupting critical cellular functions. As a platinum-containing compound, it functions as an alkylating-like agent, although its precise chemical reactions differ from classical alkylating agents. Upon passive diffusion or active transport into cells, the chloride ligands of cisplatin are displaced by water molecules in the lower intracellular chloride concentration environment, a process known as aquation. This aquation leads to the formation of highly reactive platinum species, predominantly monoaquated and diaquated forms. These activated platinum complexes then covalently bind to nucleophilic sites on DNA, most notably the N7 position of guanine residues. This binding results in the formation of various platinum-DNA adducts, including intra-strand and inter-strand cross-links, as well as DNA-protein cross-links. These adducts cause significant structural distortions and kinks in the DNA helix, which subsequently interfere with vital cellular processes such as DNA replication, transcription, and repair. The cell attempts to repair this damaged DNA; however, if the damage is extensive or irreparable, it triggers complex signal transduction pathways that ultimately lead to programmed cell death (apoptosis). This selective toxicity towards rapidly proliferating cancer cells, owing to their accelerated DNA synthesis and repair demands, forms the fundamental basis of cisplatin's therapeutic efficacy in targeting and eliminating malignant cells.
Commercial Brands (Alternatives)
No other brands found for this formula.