Effective sequencing and hydration strategies are essential for optimizing the benefits of cisplatin-based chemotherapy regimens while reducing the risk of side effects. The order in which drugs are administered—especially agents like gemcitabine, nab-paclitaxel, durvalumab, and etoposide—is guided by clinical evidence and pharmacologic principles. Timely hydration before and after cisplatin is crucial for protecting kidney function, and the sequencing of drugs can impact both blood-related toxicities and treatment effectiveness. This overview outlines the rationale and structure of several widely used cisplatin-containing regimens, emphasizing the importance of evidence-based approaches to drug sequencing and hydration in oncology care.
Gemcitabine-Cisplatin
[0-30 min] Premeds
[30-150 min] Pre-hydration
[150-180 min] Gemcitabine
[180-240 min] Cisplatin
[240-360 min] Post-hydration
Key Details from Protocols:
Gemcitabine is given first, followed by Cisplatin1,2,3. This sequence is based on clinical evidence suggesting that administering gemcitabine before cisplatin may enhance efficacy and reduce hematologic toxicity2.
Citations:
https://www.oncologynurseadvisor.com/features/drug-sequence-with-gemcitabine/
https://www.swagcanceralliance.nhs.uk/wp-content/uploads/2020/09/Cisplatin-and-Gemcitabine.pdf
Abraxane-Cisplatin-Gemcitabine
[0-30 min] Premeds
[30-150 min] Pre-hydration
[150-180 min] Abraxane (nab-paclitaxel)
[180-240 min] Cisplatin
[240-270 min] Gemcitabine
[270-390 min] Post-hydration
Key Details from Protocols:
Hydration Timing: Pre-hydration is started 30–60 minutes before chemotherapy. Post-hydration begins immediately after the last chemotherapy agent is administered1,2,3.
Sequence Rationale: The order of administration is important for efficacy and toxicity management. For example, giving gemcitabine before cisplatin may increase efficacy and reduce neutropenia, but in the nab-paclitaxel/cisplatin/gemcitabine regimen, nab-paclitaxel is given first, followed by cisplatin, then gemcitabine1,4.
Citations:
https://www.swagcanceralliance.nhs.uk/wp-content/uploads/2020/09/Cisplatin-and-Gemcitabine.pdf
https://www.oncologynurseadvisor.com/features/drug-sequence-with-gemcitabine/
Durvalumab-Cisplatin-Gemcitabine
[0-30 min] Premeds
[30-150 min] Pre-hydration
[150-210 min] Durvalumab
[210-270 min] Cisplatin
[270-300 min] Gemcitabine
[300-420 min] Post-hydration
Key Details from Protocols:
The sequence of administering cisplatin before gemcitabine when combined with durvalumab is primarily based on toxicity management and pharmacodynamic interactions:
Reduced Hematologic Toxicity:
Studies show cisplatin given 24 hours before gemcitabine (vs. the reverse) results in significantly lower rates of leukopenia3. This sequence minimizes cumulative myelosuppression, a critical factor when combining with durvalumab (an immunotherapy requiring stable blood counts)3,6.Synergistic Efficacy:
Preclinical data suggest cisplatin’s DNA-damaging effect may enhance gemcitabine’s antitumor activity when sequenced first, though clinical evidence for this specific combination with durvalumab remains under study3,5.Protocol Standardization:
In biliary tract cancer trials (e.g., TOPAZ-1), cisplatin is administered after durvalumab but before gemcitabine to align with hydration requirements and toxicity mitigation strategies6,7.
Key Trade-off: While cisplatin-first sequencing reduces leukopenia, it may slightly increase nephrotoxicity risk, necessitating rigorous hydration protocols6,7.
Citations:
https://jhoponline.com/issue-archive/2011-issues/march-vol-1-no-1/13240-top-13240
https://www.cancercareontario.ca/sites/ccocancercare/files/CISPGEMC Lung.pdf
https://www.cancerresearchuk.org/about-cancer/treatment/drugs/gc-gemcis
Bleomycin-Cisplatin-Etoposide
[0-30 min] Premeds
[30-150 min] Pre-hydration
[150-170 min] Bleomcyin
[170-230 min] Cisplatin
[230-410 min] Etoposide
[230-350 min] Post-hydration
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