Pulmonary reactions to chemotherapeutic agents: the ‘chemotherapy lung’
Philippe Camus, Edward C Rosenow in Drug-induced and Iatrogenic Respiratory Disease, 2010
The main complication of the treatment with retinoic acid is the development of the so-called ‘retinoic acid syndrome’ in approximately 25 per cent of patients receiving this medication.70–72 This capillary leak syndrome is heralded by the onset of shortness of breath, fever and diffuse pulmonary infiltrates resulting from non-cardiogenic pulmonary oedema. Pericardial and pleural effusions are also common, and may further impair the patient’s respiratory status. Hypotension and renal failure may be present as well. This syndrome usually occurs between 2 and 21 days after initiation of treatment. Its pathogenesis remains poorly understood, but it may involve a sudden massive release of cytokines by the newly differentiated myeloid cells and adhesion of matured granulocytes to the pulmonary endothelium. High leucocyte counts have been associated with an increased incidence of the retinoic acid syndrome, although inconsistently. No other obvious risk factors have been clearly identified. Microscopic examinations of affected lungs typically show diffuse infiltration by mature myeloid cells. An association with Sweet syndrome and diffuse alveolar haemorrhage has also been described.73 The mortality rate with ATRA-associated pulmonary toxicity may be as high as 9 per cent.
Other Systemic Side Effects: Cardiovascular, Pulmonary, Otolaryngorhinologic, Genitourinary, Renal, and Immunologic
Ayse Serap Karadag, Berna Aksoy, Lawrence Charles Parish in Retinoids in Dermatology, 2019
The pulmonary side effects associated with retinoids other than oral isotretinoin are quite limited. A previous study on human patients with emphysema suggested that definitive clinical improvement could not be achieved with the administration of retinoids (26). To date, three cases have been reported, where patients developed retinoic acid syndrome due to the use of acitretin for treatment of psoriasis (27–29). Retinoic acid syndrome often develops in patients receiving all-trans-retinoic acid (ATRA) therapy for promyelocytic leukemia. It is characterized by fever, acute renal failure, respiratory distress, hypotension, pleural effusion, and weight gain (30). A 63-year-old patient with significant psoriasis who developed a drug fever attributed to acitretin was reported (31). The package insert also indicates that sinusitis, coughing, increased sputum, and laryngitis may occur (19).
Use of Dermatologics during Pregnancy
“Bert” Bertis Britt Little in Drugs and Pregnancy, 2022
Studies of rats and mice born to mothers exposed to etretinate had an increased frequency of congenital anomalies consistent with the human retinoic acid embryopathy, including limb, genitourinary, neural tube, and cloacal defects (Mesrobian et al., 1994). The implication of this with regard to human teratogenicity is unknown, but adds experimental support for the retinoic acid syndrome. Obviously, this drug should not be used for psoriasis during pregnancy.
Heterogeneous Differentiation of Highly Proliferative Embryonal Carcinoma PCC4 Cells Induced by Curcumin: An In Vitro Study
Published in Nutrition and Cancer, 2021
Geetha Viswanathan, Lip Yong Chung, Usha K. Srinivas
Currently, the standard treatment option for GCT is chemotherapy in combination with etoposide, cisplatin, and bleomycin with or without surgical resection of the tumor. In addition, chemo-resistance is often a concern in GCT treatment. An alternative approach, referred to as differentiation therapy, employs a drug that reverses cell malignancy by inducing cell differentiation. A classic example of differentiation therapy is retinoic acid (RA) treatment for acute promyelocytic leukemia, an approach responsible for making this a curable form of cancer today (30). RA triggers differentiation of pluripotent cells to terminally differentiated and nonmalignant cells (31). However, RA treatment can cause retinoic acid syndrome in many patients, a syndrome characterized by symptoms that include fever, weight gain, respiratory distress, hypotension, and acute renal failure (32). Moreover, RA treatment is associated with developmental anomalies (33). Due to these potential severe side effects, the commonly used dosage of RA has been reduced from 45 to 25 mg/m2 per day (34); however, the dosage reduction reduces treatment efficacy.
Long-term follow-up of children with acute promyelocytic leukemia treated with Beijing Children’s Hospital APL 2005 protocol (BCH-APL 2005)
Published in Pediatric Hematology and Oncology, 2019
Yuanyuan Zhang, Linya Wang, Ruidong Zhang, Peijing Qi, Jing Xie, Huiwen Shi, Wei Lin, Ying Wu, Jiaole Yu, Jia Fan, Guoshuang Feng, Huyong Zheng, Minyuan Wu
The application of ATRA in the 1980s pioneered APL-targeted therapy.11 ATRA alone can increase the CR rate of APL by more than 85%, but continuous administration can cause ATRA resistance, and children with APL often relapse within 3–6 months. In addition, ATRA can induce an increase in WBC, leading to fatal retinoic acid syndrome in the early stages of treatment.12–14 The North American Collaboration Group and the European APL Group15,16 advocate ATRA combination chemotherapy as a first-line induction program, which not only reduces the incidence and mortality of retinoic acid syndrome, but also reduces the occurrence of retinoic acid resistance. The CR rate is 70%–95% and even 100% in some areas. In our study, ATRA combined with anthracycline treatment was used. The CR rates of SR and HR groups were 96.4% and 85.7%, respectively. The 10-year OS rates were 94.6% and 76.2%, respectively. Although the treatment of APL in children has been significantly improved, high rates of early mortality remain a major problem in clinical treatment. Multicenter data analysis showed early mortality rates ranging from 9.6% to 61.5%,17,18 while the number of early deaths in our study accounted for 6.5% (5/77) of patients. The lower rate observed here may be due to exclusion of patients who quit initial treatment at the beginning because of severe accompanying diseases or economic factors.
Retinoic acid associates with mortality of patients on long-term hemodialysis
Published in Renal Failure, 2022
Marta Kalousová, Miroslava Zelenková, Aleš A. Kuběna, Sylvie Dusilová-Sulková, Vladimír Tesař, Tomáš Zima
ATRA is formed from retinol in a two-step oxidation: in the first, retinol is oxidized by alcohol dehydrogenase to retinal (retinaldehyde) and in the second catalyzed by retinal dehydrogenase, retinoic acid rises. ATRA serves as a lipophilic hormone, binding to the intracellular retinoic acid receptor (RAR), and transcriptionally regulating cell proliferation, differentiation, and immune response. ATRA and its isomers have been used for many years for the treatment of psoriasis, acne, acute promyelocytic leukemia, as well as some solid tumors [3,4]. Despite beneficial effects and general good tolerability, in some cases, the treatment may be accompanied by a complication known as retinoic acid syndrome (RAS) which also includes acute renal failure [5,6]. This syndrome was described in both adults [5] and children (a case with signs of nephrotic range proteinuria) [7]. On the other hand, tissue culture and animal studies show the protective effect of ATRA on the progression of kidney damage [8]. Additionally, the role of ATRA in the reduction of atherosclerotic plaques [9] and its dose-dependent effect on cardiac remodeling [10] was also demonstrated. As data on ATRA levels in patients with renal diseases are limited [11] and cardiovascular disease is the main reason for high mortality of patients with advanced renal diseases, our aim was to measure ATRA concentrations in serum from long-term HD patients and to determine their prognostic significance.
Related Knowledge Centers
- Arsenic Trioxide
- Capillary Leak Syndrome
- Cathepsin G
- Dexamethasone
- Hypervitaminosis A
- Tretinoin
- Cytokine
- Acute Promyelocytic Leukemia