tretinoin and Stomatitis

A 34-year-old man who had been referred to our hospital was diagnosed with acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA), oral administration, was initiated. On day 25, he developed fever and respiratory distress with bilateral pulmonary infiltrates, suggesting differentiation syndrome (DS) caused by ATRA. These symptoms showed amelioration after discontinuing ATRA and initiating methylprednisolone. ATRA was re-started on day 29 at half the original dose because of residual APL blasts. The patient subsequently developed fever, severe stomatitis, and oropharyngeal ulcers, which persisted even after discontinuing ATRA. On day 48, he suddenly developed severe abdominal pain with free air, observable on an abdominal X-ray, and underwent emergency ileocecal resection. Pathological examination of the resected ileocecal intestines revealed multiple ulcers and perforations. No leukemic cell infiltration was observed. In this case, only ATRA was administered for APL treatment. These findings suggest that ileocecal ulcerations and perforations, as well as oropharyngeal ulcers, might have been caused by DS or ATRA. Furthermore, DNA typing of the HLA-B locus revealed that the patient had HLA-B51 associated with Behçet's disease. Therefore, hypercytokinemia with DS might have induced Behçet's disease-like symptoms, including stomatitis and ileocecal perforation, complications that are particularly observed in patients with HLA-B51.

Topics: Adult; Antineoplastic Agents; Cecal Diseases; HLA-B51 Antigen; Humans; Ileum; Intestinal Perforation; Leukemia, Promyelocytic, Acute; Male; Stomatitis; Tretinoin

Although retinoids show promise for prevention of second primary upper aerodigestive tract tumors, the optimum retinoid, dose, and schedule are unknown. All-trans retinoic acid (ATRA) has greater affinity for retinoic acid receptors and may be more active than other retinoids but has a shorter plasma half life and may up-regulate its own metabolism. We defined the maximum long-term tolerable dose, dosing frequency, pharmacokinetics, and toxicity of ATRA in patients with treated squamous cell carcinoma of the head and neck (SCCHN). Twenty-one patients were randomized to 45, 90, or 150 mg/m2 ATRA either once daily, or as divided doses every 8 h, for 1 year. Pharmacokinetics were assessed periodically. Fourteen men and seven women with previous SCCHN of initial stage I-IV were treated. Grade > or =3 toxicities (reversible) included headache and hypertriglyceridemia in 5 and 6 patients each, mucositis in 2 patients, and hyperbilirubinemia, elevated alkaline phosphatase, colitis, lipasemia, xerostomia, eczema, and arthritis in 1 patient each. The 150-mg/m2 dose was not tolerable. Doses were reduced for grade > or =3 toxicity in seven of eight patients at 90 mg/m2 daily. Three of nine patients at 45 mg/m2/day required dose reduction, two at the once-daily dose. Day 1 ATRA area under the plasma concentration versus time curve (AUC) increased with dose, and after 1-2 months of continued dosing, the AUC declined in 7 of 13 patients (54%) studied. ATRA AUC did not correlate with toxicity severity or frequency. Fifteen mg/m2/day every 8 h is a tolerable dose for 1 year in patients with treated SCCHN. ATRA pharmacokinetics did not correlate with toxicity.

Topics: Adult; Aged; Antineoplastic Agents; Area Under Curve; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Exanthema; Female; Follow-Up Studies; Head and Neck Neoplasms; Headache; Humans; Hypertriglyceridemia; Male; Middle Aged; Mouth Mucosa; Neoplasm Staging; Stomatitis; Treatment Outcome; Tretinoin

To evaluate a regimen including high-dose mitoxantrone in previously untreated adults with AML, 45 patients aged 21-59 (median 41) were given cytarabine, 3 g/m2 days 1-5, mitoxantrone, 80 mg/m2 day 2 and etoposide, 150 mg/m2 days 1,3,5. Post-remission therapy consisted of 5 cycles combining the same agents at reduced doses. Complete remission was seen in 36 patients. The observed 3-year survival is 28%. Cytogenetic pattern and CD34 expression correlated with response and survival. Significant toxicity included myelosuppression, mucositis, diarrhea and hyperbilirubinemia. Ventricular ejection fraction was generally reduced, with clinical cardiac dysfunction in only 2 patients. This high-dose mitoxantrone combination can be administered to young adults with AML with tolerable toxicity and results comparable to those of other dose-intensive regimens.

Topics: Actuarial Analysis; Acute Disease; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Conjunctivitis; Cytarabine; Disease-Free Survival; Etoposide; Female; Gastrointestinal Diseases; Humans; Hyperbilirubinemia; Leukemia, Myeloid; Male; Methylprednisolone; Middle Aged; Mitoxantrone; Remission Induction; Risk; Stomatitis; Stroke Volume; Survival Analysis; Survival Rate; Treatment Outcome; Tretinoin; Ventricular Dysfunction, Left

The examination of prophylactic efficacy of tretinoin on oral mucositis, post bone marrow transplantation (BMT).. The study population consisted of 11 patients undergoing BMT. Six tretinoin topically-treated patients (0.25 mg daily of 0.1% tretinoin cream) were matched with five non-treated control patients comparing mucositis severity, duration and analgetic (morphine) requirements. Concomitant follow-up included conditioning parameters associated with mucositis and engraftment.. The mean of oral mucositis peak scores was significantly lower in the tretinoin-treated patients vs the non-treated patients (score 1.5 vs 3.6; P < 0.02). In the majority of cases the duration of the most severe phase of oral mucositis was shorter in the tretinoin-treated group as compared with the control. Only one patient in the experimental group required morphine analgesics compared with four patients in the control group.. This preliminary study indicates that the severity of oral mucositis, both objective and subjective, in BMT patients may be reduced by 0.1% topical tretinoin cream, 0.25 mg, administered daily from the beginning of the BMT conditioning regimen until marrow engraftment.

Topics: Administration, Topical; Adolescent; Adult; Bone Marrow Transplantation; Child; Dental Care for Chronically Ill; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Mouth Mucosa; Pilot Projects; Stomatitis; Tretinoin

In a pilot study to reduce the duration of treatment and potential long-term toxicities, 39 patients with acute promyelocytic leukemia in remission received a single cycle of intensive consolidation therapy, followed by intermittent ATRA maintenance. Consolidation therapy required prolonged hospitalization and was associated with a high incidence of mucositis (43% grade II or greater) and documented infection (45%). No deaths occurred during consolidation. Seven patients have relapsed; all other patients are in molecular remission (median follow-up, 2.75 years). Kaplan-Meier estimate of 3 year disease-free survival is 73% (95% confidence interval 55-91%). The relapse rate (0.06 relapses/patient-year of follow-up) is well within the range of larger published series that administer more prolonged consolidation. One patient has developed secondary myelodysplastic syndrome. These pilot data suggest that decreasing the total duration of consolidation chemotherapy did not compromise disease-free survival for APL patients induced with ATRA/anthracycline and given intermittent ATRA maintenance. However, the toxicity of the consolidation module and the development of secondary myelodysplasia despite decreased total therapy emphasize the need to further improve and refine curative therapy for APL.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Humans; Incidence; Infections; Leukemia, Promyelocytic, Acute; Middle Aged; Myelodysplastic Syndromes; Neoplasm Recurrence, Local; Pilot Projects; Receptors, Retinoic Acid; Remission Induction; Retinoic Acid Receptor alpha; Reverse Transcriptase Polymerase Chain Reaction; Stomatitis; Survival Analysis; Treatment Outcome; Tretinoin

Treatment of chronic phase chronic myelogenous leukemia with hydroxyurea or busulfan rarely induces cytogenetic (true) remissions. Intensive chemotherapy induces brief true remissions in approximately 50% of patients. We added 13-cis-retinoic acid to daunorubicin, cytosine arabinoside, and thioguanine to determine if it could increase the incidence and duration of remission induced by cytotoxic chemotherapy. Of the 17 evaluable patients, one patient (6%) achieved complete remission, and seven patients (41%) achieved partial remissions. The median duration of remission was 1.6 months. We conclude that 13-cis-retinoic acid does not increase the incidence and duration of remission in chronic phase chronic myelogenous leukemia.

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Chromosomes, Human, 21-22 and Y; Cytarabine; Daunorubicin; Humans; Isotretinoin; Leukemia, Myeloid; Leukopenia; Liver; Middle Aged; Stomatitis; Thioguanine; Thrombocytopenia; Time Factors; Tretinoin