From Cisplatin to Lobaplatin: How Do 5 Major Platinum-Based Drugs Treat Cancer?

In the field of malignant tumor chemotherapy, platinum-based drugs occupy an indispensable and central position. These chemotherapeutic agents, built around platinum as their core structural element, have become first-line cornerstone treatments for a wide range of solid tumors due to their unique mechanisms of action and broad antitumor spectrum.

From first-generation cisplatin to third-generation lobaplatin, more than half a century of iterative research and development has led each platinum compound to address the shortcomings of its predecessors, achieving progressive breakthroughs in both efficacy and safety. This has resulted in a diversified yet complementary clinical application landscape.

HongKongDengyueMed will systematically elaborate on the mechanisms of action, clinical applications, and key characteristics of 5 commonly used platinum-based drugs—cisplatin, carboplatin, nedaplatin, oxaliplatin, and lobaplatin—clarifying their mechanisms of cancer cell killing and their respective clinical positioning in cancer therapy.

The Shared Anticancer Principle of Platinum-Based Drugs: Directly Targeting the “Life Code” of Cancer Cells

Although the 5 platinum-based drugs differ in structure, efficacy, and toxicity, their core anticancer mechanism is highly consistent—disrupting the DNA structure of cancer cells, preventing replication and proliferation, and ultimately inducing apoptosis. The uncontrolled proliferation of cancer cells relies on normal DNA replication, which is interrupted through a series of chemical reactions triggered by platinum compounds.

The specific pharmacological process of platinum-based drugs is illustrated as follows:Understanding the 5 Major Platinum Drugs One by One: Efficacy, Characteristics, and Clinical Applications

Starting with cisplatin, each generation of platinum drug development has focused on “enhancing efficacy, reducing toxicity, and expanding indications,” gradually resolving the limitations of earlier agents and forming complementary clinical application scenarios.

First-Generation Platinum Drug: Cisplatin — The Pioneer of Anticancer Therapy, Powerful but Highly Toxic

Cisplatin, the first-generation platinum drug, was approved in the United States in 1978. Its introduction completely transformed the landscape of cancer chemotherapy, bringing breakthrough progress particularly in the treatment of testicular and ovarian cancers. When combined with bleomycin and etoposide, cisplatin achieves an early cure rate of up to 100% in testicular cancer; in combination therapy for ovarian cancer, early cure rates can exceed 80%.

The anticancer advantages of cisplatin are highly prominent:

1.  Extremely broad anticancer spectrum: It shows significant efficacy against multiple solid tumors, including testicular cancer, ovarian cancer, lung cancer, bladder cancer, head and neck cancer, esophageal cancer, gastric cancer, and cervical cancer, and serves as a first-line chemotherapeutic agent for many cancers.

2.  Strong antitumor activity: Cisplatin binds strongly to DNA, effectively killing cancer cells, and exhibits synergistic effects with various other antitumor drugs, enhancing overall therapeutic outcomes.

3.  Low cost and high cost-effectiveness: It is suitable for use in primary healthcare institutions and for patients with limited financial resources.

However, the limitations of cisplatin are equally evident, particularly its severe toxic reactions, which require close attention in clinical practice. Its primary dose-limiting toxicity is nephrotoxicity. Approximately 90% of the drug is excreted via the kidneys and less than 10% via the biliary tract, which can cause renal tubular damage, manifested by elevated blood urea nitrogen and serum creatinine levels. Repeated high-dose use may result in irreversible renal injury. Therefore, adequate hydration therapy is required prior to administration to increase urine output and reduce nephrotoxicity.

In addition, cisplatin causes severe gastrointestinal toxicity: approximately 80% of patients experience significant nausea and vomiting, necessitating the use of potent antiemetic drugs. Ototoxicity is also pronounced, potentially leading to high-frequency hearing loss and tinnitus, which may be irreversible. Mild bone marrow suppression and peripheral neurotoxicity may also occur, presenting as leukopenia and numbness in the extremities.

Second-Generation Platinum Drug: Carboplatin — An “Improved Version” of Cisplatin with Lower and Milder Toxicity

To overcome the severe toxicity of cisplatin, scientists modified its structure and introduced the second-generation platinum drug carboplatin in 1986. Carboplatin has a chemical structure similar to cisplatin and shares the same anticancer mechanism, but with optimized efficacy and toxicity, making it one of the most widely used platinum drugs in clinical practice.

The core advantage of carboplatin is its significantly reduced toxicity: nephrotoxicity, ototoxicity, and gastrointestinal toxicity are markedly lower than those of cisplatin. Complex hydration therapy is generally unnecessary during clinical use, greatly improving patient tolerability. It is particularly suitable for elderly patients, patients with impaired hepatic or renal function, and those unable to tolerate cisplatin.

At the same time, carboplatin has an anticancer spectrum largely consistent with cisplatin. Tumors sensitive to cisplatin often respond well to carboplatin. As monotherapy, carboplatin achieves cure rates of up to 60% in non-small cell lung cancer (NSCLC). In combination with paclitaxel, etoposide, and other agents, it is used in the treatment of ovarian cancer, lung cancer, head and neck cancer, and other malignancies. In NSCLC, survival outcomes are not significantly different from those achieved with cisplatin.

However, carboplatin has its own limitations. Its bone marrow suppression is more pronounced than that of cisplatin and represents its primary dose-limiting toxicity. This manifests as leukopenia and thrombocytopenia, typically reaching a nadir 14–24 days after administration and gradually recovering within 35–41 days. Severe cases may lead to infection or bleeding complications, necessitating regular blood count monitoring and dose adjustment based on bone marrow function. In addition, carboplatin exhibits cross-resistance with cisplatin; patients resistant to cisplatin may experience reduced efficacy with carboplatin. Its antitumor activity is slightly lower than that of cisplatin, and efficacy may be suboptimal in certain advanced or refractory tumors.

Second-Generation Platinum Drug: Nedaplatin — Targeting Head and Neck Cancers with Minimal Gastrointestinal Toxicity

Nedaplatin, approved in Japan in 1995, is another second-generation platinum drug derived from structural modification of cisplatin. Its development focused on further toxicity optimization while enhancing efficacy against specific tumors, particularly head and neck cancers. It has been included in the Class B National Reimbursement Drug List.

Key characteristics of nedaplatin include:

● Extremely mild gastrointestinal toxicity: The incidence and severity of nausea and vomiting are significantly lower than with cisplatin and carboplatin, resulting in better patient tolerability without the need for potent antiemetics.

● Notable efficacy against squamous cell carcinoma: It is particularly suitable for head and neck squamous cell carcinomas (such as laryngeal, nasopharyngeal, and oral cancers). It can be used alone or in combination with radiotherapy or other chemotherapeutic agents to effectively reduce tumor size, alleviate symptoms, and improve survival and quality of life.

● Certain efficacy in other solid tumors, including small cell lung cancer, non-small cell lung cancer, esophageal cancer, and ovarian cancer.

The limitations of nedaplatin are mainly reflected in bone marrow suppression, similar to carboplatin, characterized by leukopenia and thrombocytopenia and serving as its dose-limiting toxicity. Regular blood count monitoring is required during treatment.

Although nephrotoxicity and ototoxicity are lower than with cisplatin, a small number of patients—especially those with prior cisplatin exposure or renal impairment—may still experience renal dysfunction or hearing loss, requiring cautious use. Its anticancer spectrum is relatively narrower, with less efficacy against ovarian and bladder cancers compared with cisplatin and carboplatin, and some degree of cross-resistance with cisplatin exists.

Third-Generation Platinum Drug: Oxaliplatin — Overcoming Resistance and Targeting Gastrointestinal Tumors

Oxaliplatin, a third-generation platinum drug, was launched in France in 1996. Its structure differs substantially from earlier platinum drugs, with its most significant breakthrough being the absence of cross-resistance with cisplatin and carboplatin. It is particularly effective against gastrointestinal tumors, fundamentally transforming the chemotherapy landscape for colorectal and other gastrointestinal cancers. It is currently a Class B reimbursed drug and is widely used in clinical practice.

The core advantages of oxaliplatin are highly distinct:

1.  Significant efficacy against gastrointestinal tumors

2.  No cross-resistance with cisplatin or carboplatin

3.  Extremely low nephrotoxicity and ototoxicity

The main limitation of oxaliplatin is peripheral neurotoxicity, which is its most typical and primary dose-limiting toxicity. This neurotoxicity can be classified as acute or chronic:

● Acute neurotoxicity manifests as numbness and sensory abnormalities in the hands and feet within hours after administration, exacerbated by cold exposure, and usually resolves within 1–2 weeks.

● Chronic neurotoxicity presents as long-term, persistent numbness and sensory loss in the extremities, which may impair limb function and can be irreversible in severe cases.

Therefore, strict dose control is required in clinical use, and concomitant administration with other neurotoxic drugs should be avoided. Patients should be advised to keep warm and avoid contact with cold water. Although oxaliplatin causes less gastrointestinal toxicity than cisplatin, some patients may still experience nausea, vomiting, or diarrhea, which can be managed with appropriate supportive care. Bone marrow suppression is generally mild, and most patients tolerate treatment without frequent dose adjustments.

Third-Generation Platinum Drug: Lobaplatin — A Chinese Innovation with Milder Toxicity and Broad Applicability

Lobaplatin, approved in China in 2005, is a third-generation platinum drug independently developed in China. Its structure has been further optimized to achieve superior toxicity control while maintaining a broad anticancer spectrum and flexible clinical applicability.

The core advantages and indications of lobaplatin include:

● Mild toxicity and good tolerability: Nephrotoxicity, ototoxicity, and peripheral neurotoxicity are extremely low, and no hydration therapy or special nursing care is required.

● Mild adverse reactions: The incidence of nausea and vomiting is 34.3%, with only 6.7% of patients experiencing severe vomiting, indicating high tolerability.

● Relatively mild bone marrow suppression, mainly manifested as thrombocytopenia, with a low incidence of leukopenia that can be alleviated with symptomatic treatment.

● Broad patient applicability, especially suitable for elderly patients, those with frail constitutions, and patients with hepatic or renal dysfunction.

● Broad anticancer spectrum, with significant efficacy against breast cancer, small cell lung cancer, and chronic myelogenous leukemia, and applicability in ovarian and cervical cancers.

The limitations of lobaplatin include slightly lower anticancer activity compared with cisplatin and oxaliplatin, potentially reduced efficacy in advanced or refractory tumors, and some degree of cross-resistance with cisplatin and carboplatin. Its relatively higher cost may increase the long-term economic burden compared with cisplatin and carboplatin. In addition, a small number of patients may experience allergic reactions, such as purpuric rash or skin flushing, requiring close monitoring during treatment.

Core Comparison of the 5 Platinum Drugs: How to Choose the Appropriate Agent?

Each of the 5 platinum drugs has its own strengths and limitations. Clinical selection should be based on tumor type, disease stage, patient physical condition, prior treatment history, and economic considerations. A summary comparison is as follows:

Clinical Misconceptions and Precautions in the Use of Platinum Drugs

Despite their significant efficacy, platinum drugs must be used judiciously to maximize benefits and minimize toxicity:

1.  Lower toxicity is not always better: Drug selection should prioritize tumor–drug compatibility. For example, oxaliplatin remains the first choice for colorectal cancer despite its neurotoxicity, while lobaplatin or carboplatin may be more appropriate for frail elderly patients.

2.  Beware of drug resistance: Long-term use of a single platinum drug may lead to resistance. Combination chemotherapy or alternating platinum agents is often employed to delay resistance, with regular reassessment and timely adjustment of treatment strategies.

3.  Emphasize toxicity monitoring and supportive care: Hydration and renal and auditory monitoring are essential with cisplatin; blood counts should be monitored with carboplatin and nedaplatin; cold avoidance is important with oxaliplatin; and allergic reactions should be monitored with lobaplatin.

4.  Caution in special populations: Platinum drugs should be used cautiously in pregnant or breastfeeding women, patients with severe hepatic or renal dysfunction, or severe bone marrow suppression. Dose adjustments and enhanced monitoring are required in elderly patients, and safety in pediatric populations has not been fully established.

Conclusion: The Evolution of Platinum Drugs Represents Continuous Breakthroughs in the Fight Against Cancer

From the pioneering application of cisplatin, through toxicity optimization with carboplatin and nedaplatin, to breakthroughs in resistance and targeting with oxaliplatin and lobaplatin, the iterative development of these 5 commonly used platinum drugs reflects ongoing progress in cancer therapy. While they share a core anticancer mechanism, their distinct pharmacological characteristics allow them to address different tumor types and patient conditions, making them cornerstone agents in clinical oncology chemotherapy.

Looking ahead, continued scientific exploration is expected to bring further breakthroughs within the platinum drug family, offering renewed hope to more cancer patients. For patients, understanding the characteristics and applications of platinum drugs, actively cooperating with medical treatment plans, and maintaining an optimistic mindset remain key to overcoming cancer.

Global pharmaceutical wholesaler DengyueMed, guided by its mission to “connect global pharmaceutical companies with end markets,” adheres to innovation-driven and quality-first principles, promoting equitable access to medicines and providing the support and care patients need.