Metastatic colorectal cancer and severe hypocalcemia following irinotecan administration in a patient with X-linked agammaglobulinemia: a case report

Abstract

Background X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by germline mutations in the Bruton tyrosine kinase (BTK) gene on X chromosome. These mutations disturb B-cell development, decrease immunoglobulin levels, increase susceptibility to infection or neoplasms, and increase the risk of developing colorectal cancer (CRC). For occasional cases of CRC have been reported in XLA patients, low levels of B lymphocytes and immunoglobulins induced by congenital immune disorder make them more susceptible to drug-related toxicities (DRT). Therefore, gene sequencing, therapeutic drug monitoring and any possible measurement to predict DRT should be considered before determining the course of chemotherapy for XLA patients with CRC. Case presentation In this study, we reported a 21-year-old male who developed metastatic CRC in the context of XLA. Since the whole exome sequencing and therapeutic drug monitoring did not reveal any predictive markers of DRT, we applied standard first-line chemotherapy to the patient. However, progressive disease occurred after the fifth treatment cycle. Therefore, the administration of oxaliplatin was changed to irinotecan as second-line therapy. After that, the patient firstly suffered from severe hypocalcemia and eventually died due to metastatic CRC after the eighth treatment cycle. The overall survival time was 7.5 months. Conclusions This study reported the first written record of a Chinese XLA patient with metastatic CRC and severe hypocalcemia. Whole exome sequencing and bioinformatic analysis indicated the somatic mutations in ABCA6, C6 and PAX3 genes might contribute to the early-onset and metastasis CRC. Besides, a number of germline mutations in genes related to calcium metabolism (CACNA2D4, CD36, etc.) and the administration of irinotecan were speculated to be the causes of severe hypocalcemia. We therefore suggested that in order to avoid severe DRT, clinicians should take genetic background and therapeutic drug monitoring into consideration while planning chemotherapy treatment for XLA patients with CRC.

Development of an Immune Infiltration-Related Eight-Gene Prognostic Signature in Colorectal Cancer Microenvironment

“…Our results showed that CD36 was significantly downregulated in CRC tissues compared to normal tissues, which was validated in vitro and in vivo [ 26 ]. Genome-wide DNA methylation analysis revealed that hypermethylation of CD36 could contribute to its low expression [ 27 ]. Fang et al found that CD36 expression gradually decreased from adenoma to cancer and CD36 loss implied a poor prognosis in patients with CRC [ 28 ].…”

Cleavage-defective Topoisomerase I mutants sharply increase G-quadruplex-associated genomic instability

“…The resulting genomic rearrangements originating at G4-motifs may lead to secondary cancer development greatly complicating patient treatment. Other studies have documented secondary cancer development in patients following treatment with CPT-derivatives [ 68 , 69 ]. In the future, it will be valuable to explore how CPT-treatment and subsequent emergence of Top1 mutants can lead to further genome instability and potential secondary cancers.…”

Current Status of Therapeutic Drug Monitoring of 5-Fluorouracil Prodrugs

“…At present, TDM is being performed to elucidate the pharmacokinetic properties of drugs. However, there are some case reports of dose adjustment of 5-FU prodrugs by TDM (Table II) (48)(49)(50)(51)(52). Tanaka reported that TDM of S-1 was used in patients with recurrent gastric cancer undergoing maintenance dialysis to estimate the appropriate S-1 dose and administer treatment.…”

“…Yoshida performed TDM of capecitabine in a colon cancer patient with DPD deficiency, and the dose was adjusted while observing side effects (51). Li reported that TDM of capecitabine was performed in immunodeficient X-linked agammaglobulinaemia colorectal cancer patients, and the dose was adjusted while focusing on the appearance of toxicity (52).…”