Cytokine profiling, pretreatment with anakinra, and tolerance development in platinum-induced mixed hypersensitivity reactions.

BACKGROUND: Cytokine-release reactions (CRR) induced by platinum-based chemotherapy, manifesting with fever, chills, and rigors, are poorly understood and not easily prevented by usual premedication or desensitization. OBJECTIVE: To gain a better understanding of platinum-induced CRR and to explore the use of anakinra as a tool to prevent its clinical manifestations. METHODS: A cytokine and chemokine panel was obtained before and after platinum infusion in 3 cases with a mixed (immunoglobulin E-mediated and CRR) platinum-induced hypersensitivity reaction and in 5 controls either tolerant or with an immunoglobulin E-mediated platinum-induced hypersensitivity reaction. Anakinra was given as premedication in the 3 CRR cases. RESULTS: Cytokine-release reaction was associated with a marked release of interleukin (IL)-2, IL-5, IL-6, IL-10, and tumor necrosis factor-ɑ in all cases whereas only IL-2 and IL-10 increased in some controls after platinum infusion, and to a lesser extent than in cases. Anakinra seemed to block CRR symptoms in 2 cases. In the third case, who initially had CRR symptoms despite anakinra, tolerance to oxaliplatin appeared to develop after repeated re-exposures, as suggested by the decreasing levels of cytokines after oxaliplatin, except IL-10, and the capacity to progressively shorten the desensitization protocol and taper the premedication, in addition to the negativization of the oxaliplatin skin test result. CONCLUSION: In patients with platinum-induced CRR, anakinra could be a useful premedication to block its clinical manifestations, and monitoring of IL-2, IL-5, IL-6, IL-10, and tumor necrosis factor-ɑ could help predict tolerance development, thereby allowing safe adjustments to the desensitization protocol and premedication.

Implementing DPYD*2A Genotyping in Clinical Practice: The Quebec, Canada, Experience.

BACKGROUND: Fluoropyrimidines are used in chemotherapy combinations for multiple cancers. Deficient dihydropyrimidine dehydrogenase activity can lead to severe life-threatening toxicities. DPYD*2A polymorphism is one of the most studied variants. The study objective was to document the impact of implementing this test in routine clinical practice. METHODS: We retrospectively performed chart reviews of all patients who tested positive for a heterozygous or homozygous DPYD*2A mutation in samples obtained from patients throughout the province of Quebec, Canada. RESULTS: During a period of 17 months, 2,617 patients were tested: 25 patients tested positive. All were White. Twenty-four of the 25 patients were heterozygous (0.92%), and one was homozygous (0.038%). Data were available for 20 patients: 15 were tested upfront, whereas five were identified after severe toxicities. Of the five patients confirmed after toxicities, all had grade 4 cytopenias, 80% grade ≥3 mucositis, 20% grade 3 rash, and 20% grade 3 diarrhea. Eight patients identified with DPYD*2A mutation prior to treatment received fluoropyrimidine-based chemotherapy at reduced initial doses. The average fluoropyrimidine dose intensity during chemotherapy was 50%. No grade ≥3 toxicities were observed. DPYD*2A test results were available in an average of 6 days, causing no significant delays in treatment initiation. CONCLUSION: Upfront genotyping before fluoropyrimidine-based treatment is feasible in clinical practice and can prevent severe toxicities and hospitalizations without delaying treatment initiation. The administration of chemotherapy at reduced doses appears to be safe in patients heterozygous for DPYD*2A. IMPLICATIONS FOR PRACTICE: Fluoropyrimidines are part of chemotherapy combinations for multiple cancers. Deficient dihydropyrimidine dehydrogenase activity can lead to severe life-threatening toxicities. This retrospective analysis demonstrates that upfront genotyping of DPYD before fluoropyrimidine-based treatment is feasible in clinical practice and can prevent severe toxicities and hospitalizations without delaying treatment initiation. This approach was reported previously, but insufficient data concerning its application in real practice are available. This is likely the first reported experience of systematic DPYD genotyping all over Canada and North America as well.

Incidence of scalp metastases in breast cancer: a retrospective cohort study in women who were offered scalp cooling.

Scalp cooling is an intervention used to decrease the degree of chemotherapy-induced alopecia. The objective is to determine the incidence of scalp metastases among women with early breast cancer who received neoadjuvant or adjuvant chemotherapy. We conducted a retrospective cohort study of women with breast carcinoma diagnosed between June 1, 1998 and June 30, 2002. The median follow-up was 5.8 years (+/-1.7) for the scalp cooling group (n = 553) and 5.4 years (+/-1.7) for the non-scalp cooling group (n = 87). The incidence of scalp metastases was 1.1% (6 cases out of 553 patients) among women who used scalp cooling in the neoadjuvant or adjuvant setting and 1.2% also (1 case out of 87 patients) among women who did not use scalp cooling in the neoadjuvant or adjuvant setting. The incidence of scalp metastases was low and no case presented as an isolated site of relapse.

Evaluation of factors associated with recruitment in hematological clinical trials: a retrospective cohort study.

The objectives of this study were to measure the recruitment, to study characteristics associated with recruitment, and to explore reasons for non-recruitment in clinical trials for malignant hematological diseases. Trials opened between 2002 and 2008 were selected. If the patient fulfilled the main criteria of the protocol, all eligibility criteria of the protocol were assessed. A total of 1394 patients-protocol were identified in 17 protocols (697 patients, since a patient could have been eligible for more than one protocol) and 195 patients-protocol (186 patients) of these fulfilled the main criteria of the protocol. Among the 195 patients-protocol, 133 (68·2%) fulfilled all the eligibility criteria and 45 (23·1%) were recruited. Patients, physicians, and protocol characteristics were not associated with recruitment. The most common reasons for not being recruited were as follow: 40·7%, not fulfilling all eligibility criteria; 31·3%, protocol not being proposed according to the chart; and 22·7%, patients' refusal.