carboplatin

Overview

Carboplatin is a second-generation platinum compound that, like cisplatin, forms intrastrand and interstrand DNA crosslinks via platination of guanine residues, inducing replication-fork stalling and apoptosis. It is FDA-approved for ovarian cancer and is used broadly in combination chemotherapy for lung, head and neck, and other solid tumors. Compared with cisplatin it has a more favorable toxicity profile (less nephrotoxicity, ototoxicity, and nausea) at the cost of greater myelosuppression. In the UCLA sarcoma PDTO screen it was included in the >400-compound drug panel.

Evidence in the corpus

  • Carboplatin is listed in the UCLA sarcoma PDTO drug library (sarcoma_ucla_2024, n=194 specimens from 126 patients across 24 subtypes). The paper reports that 59% of specimens (57/97) and 58% of patients (43/74) had at least one FDA-approved or NCCN-recommended top-five regimen identified by the screen; carboplatin was among the compounds contributing to this actionability landscape across sarcoma subtypes. PMID:39305899
  • Used as part of platinum-based chemotherapy for metastatic urothelial carcinoma in the UC-GENOME study (n=218); ERCC2 mutations associated with significantly higher chemotherapy response rate (p=0.0134) PMID:36333289
  • Prior platinum (carboplatin) exposure in ovarian MiNEN patient PN19 (11 months prior) generated platinum-therapy mutational signatures detected by WGTA in the POG NEN cohort PMID:24326773
  • Used as part of platinum-based chemoimmunotherapy backbone in R/M NPC trials cited in this review PMID:24952746
  • In muscle-invasive bladder cancer patients ineligible for cisplatin, carboplatin-based regimens are proposed as candidates for study in ERCC2-mutant tumors, given the mechanistic link between ERCC2 loss-of-function and platinum sensitivity PMID:25096233
  • In 20 mCRPC men treated with carboplatin (from the prad_fhcrc rapid-autopsy cohort), those with a somatic DNA-repair pathway aberration (homozygous loss in any FA-pathway gene or hetero-/homozygous inactivating event in ATM) had significantly longer time on carboplatin (log-rank P = 0.02), supporting platinum-based therapy in DNA-repair-deficient mCRPC. PMID:26928463
  • Platinum chemotherapy; usable from second trimester in pregnant young-onset NSCLC patients when combined with taxanes or vinca alkaloids; recommended as pregnancy-compatible alternative to cisplatin in this review PMID:27346245
  • Adjuvant cisplatin/carboplatin plus vinorelbine was the standard adjuvant backbone in the TRACERx NSCLC ctDNA study (NCT01888601, n=24 longitudinal patients); ctDNA clearance after adjuvant therapy correlated with sustained remission while rising ctDNA burden identified platinum-resistance in real time. PMID:28445469

Resistance mechanisms

  • Not specifically characterized in the sarcoma corpus.

Cancer types (linked)

  • OS, LMS, RMS, CHDM — sarcoma subtypes included in the pan-sarcoma PDTO screen.
  • NSCLC — adjuvant cisplatin/carboplatin + vinorelbine in TRACERx; platinum resistance detectable by rising ctDNA burden.

Sources

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