tretinoin and Headache

Topics: Abnormalities, Drug-Induced; Adult; Alitretinoin; Anti-Inflammatory Agents; Capsules; Clinical Trials as Topic; Contraception; Contraindications; Drug Administration Routes; Drug Costs; Eczema; Female; France; Headache; Humans; Hyperlipidemias; Immunologic Factors; Male; Pregnancy; Retinoid X Receptors; Social Security; Tretinoin

Alitretinoin (9-cis-retinoic acid) is an endogenous derivative of vitamin A and functions as an agonist of both families of nuclear receptors (retinoic acid receptor-α, -β, -γ; retinoid X receptor-α, -β, -γ). It has been investigated in the treatment of chronic hand eczema in many studies in recent years and the results have been promising.. To evaluate the efficacy and safety of oral alitretinoin in the treatment of chronic hand eczema that is refractory to treatment with potent topical corticosteroids and to analyze the long-term response to treatment.. A prospective, observational, descriptive study was undertaken in 15 patients with chronic hand eczema that was refractory to treatment with potent topical corticosteroids. Patients were administered oral alitretinoin 30 mg/d for 3 months followed by 6 months of follow-up.. A complete response, with "clear" hands was obtained in 7 patients (47%), 5 patients (33%) achieved a partial response (almost clear hands), 1 patient (7%) showed substantial improvement, 1 (7%) showed moderate improvement, and 1 patient (7%) did not respond to treatment. Relapse occurred within 6 months of treatment suspension in 54% of cases. The treatment was well tolerated. Side effects, observed in 50% of cases, were mild (headache, elevated lipid levels, slightly elevated transaminase levels, and epigastric pain), except in 1 patient, who had a substantial reduction in thyroid stimulating hormone levels.. The results of our study support the proposal of alitretinoin as an effective and safe short-term and medium-term treatment for chronic hand eczema in patients whose disease is refractory to treatment with potent topical corticosteroids.

Topics: Administration, Cutaneous; Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Alitretinoin; Child; Chronic Disease; Drug Resistance; Eczema; Female; Hand Dermatoses; Headache; Humans; Hypercholesterolemia; Middle Aged; Occupational Diseases; Prospective Studies; Thyrotropin; Treatment Outcome; Tretinoin

Seventy-six patients with acute promyelocytic leukemia (APL) in first complete remission after induction and consolidation by daunorubicin and cytosine arabinoside received oral arsenic trioxide (As(2)O(3))-based maintenance. Three regimens were used: oral As(2)O(3) (10 mg/day, regimen A, n = 20), oral As(2)O(3) plus all-trans retinoic acid (ATRA, 45 mg/m(2) per day, regimen AA, n = 19), and oral As(2)O(3) plus ATRA plus ascorbic acid (1000 mg/day, regimen AAA, n = 37), each given for 2 weeks every 2 months for 2 years. Patients receiving A, AA, and AAA maintenance did not differ significantly in clinicopathologic features and risk factors. Headache, dyspepsia, reversible liver function derangement, and herpes zoster reactivation were adverse effects observed during maintenance. QTc prolongation and arrhythmias were not encountered. At a median follow-up of 24 months (range, 1-115 months), there were 8 relapses. The 3-year leukemia-free-survival, event-free-survival, and overall-survival were 87.7%, 83.7%, and 90.6%, respectively. Adverse prognostic factors included male gender for leukemia-free-survival, and unrelated cancers for overall survival. Age, presentation WBC count and platelet count, and the type of oral As(2)O(3) maintenance regimens had no impact on survivals. Prolonged oral As(2)O(3) maintenance was feasible and safe and resulted in favorable outcomes when used with a simple induction and consolidation regimen compared with other protocols composed of multiple chemotherapeutic agents.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Arsenicals; Ascorbic Acid; Cytarabine; Daunorubicin; Disease-Free Survival; Dyspepsia; Female; Follow-Up Studies; Headache; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Oxides; Recurrence; Remission Induction; Time Factors; Treatment Outcome; Tretinoin

To determine the maximum tolerated dose and describe the toxicities of 9-cis-retinoic acid (9cRA, ALRT1057) administered p.o. tid in pediatric patients with refractory cancer and to study the pharmacokinetics of 9cRA and determine whether systemic drug exposure changes with chronic dosing.. Children with refractory cancer (stratified by age, < or =12 and >12 years) were treated with p.o. 9cRA for 28 consecutive days. The starting dose was 50 mg/m(2)/day divided into 3 doses with planned escalations to 65, 85, and 110 mg/m(2)/day. Pharmacokinetic sampling was performed on days 1 and 29 of the first cycle.. Of the 37 patients entered, 18 patients < or =12 years of age and 11 patients >12 years of age were evaluable for toxicity. In patients >12 years of age, dose-limiting headache occurred in 2/2 patients at the 110 mg/m(2)/day dose level; 1/8 patients at 85 mg/m(2)/day developed dose-limiting pseudotumor cerebri. In patients < or =12 years of age, 3/5 patients at the starting dose level of 50 mg/m(2)/day developed dose-limiting pseudotumor cerebri; and 0/6 patients experienced dose-limiting toxicity at 35 mg/m(2)/day. Reversible non-dose-limiting hepatotoxicity was observed in 15 patients across all of the dose levels. There was considerable interpatient variability in 9cRA plasma concentrations. Peak plasma concentrations of 9cRA occurred at a median of 1.5 h after a p.o. dose, and the harmonic-mean terminal half-life was 43 min. By day 29 of 9cRA administration, the plasma 9cRA area under the curve declined by an average of 65% from day 1 values.. The dose-limiting toxicity of 9cRA in pediatric patients was neurotoxicity, primarily pseudotumor cerebri. Younger children tolerate significantly lower doses of 9cRA than older children. Similar to all-trans-retinoic acid, the pharmacokinetics of 9cRA demonstrated a wide degree of interpatient variability and decreased over time when administered on a daily basis. The recommended Phase II dose of 9cRA in patients < or =12 and >12 years of age is 35 and 85 mg/m(2)/day, respectively.

Topics: Adolescent; Adult; Age Factors; Alitretinoin; Antineoplastic Agents; Area Under Curve; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Headache; Humans; Liver; Male; Nausea; Neoplasms; Skin Diseases; Transaminases; Treatment Outcome; Tretinoin; Triglycerides; Vomiting

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

In addition to suppressing breast cancer cell growth, retinoids potentiate growth inhibition in human breast cancer when tested in vitro and in vivo with tamoxifen and/or interferon. The purpose of this study was to ascertain the biologic effects of all-trans-retinoic acid (ATRA) administered alone and with tamoxifen +/- interferon and to identify the relationship between ATRA plasma concentrations and optimal biological dose (the lowest dose that produces a biological response). Three consecutive groups of 15 patients with locally advanced operable breast cancer were treated, in accordance with good clinical practice (GCP) requirements, with ATRA at 3 dose levels alone or with tamoxifen +/- alpha-interferon 2a at flat doses. After 3 weeks, the tumors were surgically removed. Biological parameters measured at the beginning (in biopsy tissue) and end (in surgical tissue) of the study were compared. The optimal biological dose for ATRA was 15 mg/m2/day. Treatments influenced tumor grade but not cell cycle kinetics (G0-G1 phase) or proliferation (Ki67 levels). ATRA induced progesterone receptors independent of dose level and co-administered drugs, but did not induce estrogen receptors when administered alone. Retinoic acid receptor (RAR)-alpha was not affected by treatment and RAR-alpha was moderately influenced whereas RAR-beta (concomitantly with transforming growth factor-beta) was induced in 33% of patients by ATRA alone. ATRA pharmacokinetics were dose- and time-dependent. Neither the ATRA + tamoxifen nor the ATRA + tamoxifen + interferon combinations potentiated the ATRA-induced biological changes. Future studies evaluating the role of RAR-beta as a biological marker of retinoid activity are warranted.

Topics: Aged; Aneuploidy; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Bone Marrow Diseases; Breast Neoplasms; Carcinoma; Drug Administration Schedule; Drug Interactions; Female; Follow-Up Studies; Headache; Humans; Hypercholesterolemia; Interferon alpha-2; Interferon-alpha; Ki-67 Antigen; Mastectomy; Middle Aged; Neoplasm Proteins; Receptors, Retinoic Acid; Receptors, Steroid; Recombinant Proteins; Safety; Tamoxifen; Transforming Growth Factor beta; Transforming Growth Factor beta1; Treatment Outcome; Tretinoin

9-cis-Retinoic acid (9-cis-RA) has a particular pattern of binding and activating retinoid receptors. Treatment of chronic hand eczema is often refractory to conventional treatment.. Evaluation of oral 9-cis-RA therapy in chronic hand eczema in a pilot study.. Thirty-eight patients with refractory chronic hand eczema were treated in an exploratory open-label study with oral 9-cis-RA.. Twenty-one (55%) showed a very good response, 13 (34%) a good response, 2 (5.5%) a moderate response and 2 (5.5%) no response. Side effects were mild.. 9-cis-RA is a valuable drug when given at low doses to patients with chronic hand eczema.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Alitretinoin; Antineoplastic Agents; Cheilitis; Chronic Disease; Eczema; Female; Flushing; Hand Dermatoses; Headache; Humans; Male; Middle Aged; Patient Satisfaction; Pilot Projects; Severity of Illness Index; Skin; Treatment Outcome; Tretinoin

Malignant gliomas continue to be a significant source of mortality in young and middle aged adults. The introduction of new treatment strategies and multidisciplinary approaches has improved the outcome of patients with these tumors only slightly. Because retinoic acid has growth inhibitory activity against glioma and neuroblastoma cells in cultures, we assessed the efficacy of all-trans-retinoic acid in the treatment of recurrent cerebral gliomas. Thirty-six patients with recurrent cerebral gliomas were entered in the study and treated with 120 or 150 mg/ m2/day of all-trans-retinoic acid as a single agent. The drug was given for 3 weeks followed with one week of rest. Two blocks of 4 weeks constituted one course of treatment. One (3%) of 34 evaluable patients had a minor response and 14 (41%) had stable disease. In the rest of the patients (56%), tumors continued to progress despite treatment. The median time to progression of all evaluable patients was 8 weeks, and for the responders was 17 weeks. The higher dose level (150 mg/m2) was associated with high incidence of headache, which responded to dose reduction. The lower dose level was very well tolerated, with mild, mainly dermatological toxicity. All-trans-retinoic acid as a single agent has no significant activity against recurrent cerebral gliomas.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Brain Neoplasms; Child; Child, Preschool; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Glioma; Headache; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Skin; Time Factors; Tretinoin

It is generally accepted that the inhibition of sebum excretion has a predictive value for anti-acne activity. Whereas oral 13-cisretinoic acid (13-cis-RA) decreases sebum excretion, it has not been shown so far if oral all-trans-retinoic acid (tretinoin, tRA) does so. The aim of this exploratory study was to investigate the effect of oral tRA on the sebum excretion rate (SER) in young male subjects.. 12 healthy volunteers with a baseline SER above 1.0 microgram/cm2/min were treated with 20 mg/day tRA for 4 weeks. The SER was measured at weeks 2 and 4. Adverse reactions were recorded.. The mean SER varied from 1.56 at baseline to 1.65 at week 2 and to 1.49 micrograms/cm2/min at week 4. Comparison with values obtained in the same subjects previously treated with either 13-cis-RA or 9-cis-retinoic acid indicated that tRA less sebosuppressive. Mucocutaneous reactions and headache were the most frequent side effects of oral tRA.. The lack of effect on the SER suggests that oral tRA would probably be ineffective against acne. The fact that, of the three isomers tested, only 13-cis-RA (which does not bind to nuclear receptors) shows activity may suggest that sebosuppression is not nuclear receptor mediated. We discuss other hypotheses related to pharmacokinetics.

Topics: Acne Vulgaris; Administration, Oral; Adult; Alitretinoin; Drug Eruptions; Facial Dermatoses; Headache; Humans; Isotretinoin; Keratolytic Agents; Lip Diseases; Male; Mucous Membrane; Retinoids; Sebum; Skin; Tretinoin

A phase I/II study of oral all-trans-retinoic acid (ATRA; tretinoin), administered every other week alone and then in combination with interferon (IFN) alfa-2a, was undertaken to evaluate the activity, toxicity, and pharmacokinetics of this regimen in patients with human immunodeficiency virus (HIV)-associated Kaposi's sarcoma (KS).. Thirteen patients with HIV-associated KS, eight of whom had more than 100 CD4 cells/microL, were entered. The protocol initially called for patients to receive 150 mg/m2/d of ATRA every other week. However, this regimen was associated with headaches, and the initial dose of ATRA was reduced to 40 mg/m2/d orally in three divided doses, increasing to a maximum of 100 mg/m2/d. After 12 weeks, IFN alfa-2a could be added.. The principal toxicities from ATRA were headaches (12 patients) and dry skin or lip (seven patients). Of 12 assessable patients, 10 had progressive disease and two had stable disease on ATRA alone. One of eight assessable patients who went on to receive ATRA plus IFN alfa-2a had partial response (PR). There were no overall changes in the serum HIV p24 antigen (Ag) level or CD4 count during treatment with ATRA alone. Peak ATRA levels decreased during the week of continuous ATRA therapy, but rebounded when treatment was resumed after a week without the drug.. Intermittent ATRA therapy was reasonably well tolerated and provided a means to circumvent the low plasma exposure found with continuous ATRA therapy. However, we were unable to document antitumor activity in patients with HIV-associated KS.

Topics: Adult; Combined Modality Therapy; Drug Administration Schedule; Headache; HIV; HIV Infections; Humans; Interferon alpha-2; Interferon-alpha; Least-Squares Analysis; Male; Middle Aged; Recombinant Proteins; Regression Analysis; Remission Induction; Sarcoma, Kaposi; Tretinoin; Virus Replication

Prompted by recent demonstrations that all-trans-retinoic acid (all-trans-RA) had efficacy in acute promyelocytic leukemia, a phase I trial of all-trans-RA was conducted to establish the maximum-tolerated dose (MTD) before phase II testing.. Forty patients with a histologic or cytologic diagnosis of malignancy other than leukemia were treated with single daily oral doses of all-trans-RA ranging from 45 mg/m2 to 200 mg/m2. Doses of all-trans-RA were escalated in the next cohort of patients until the MTD was determined if the preceding dose level was not associated with significant toxicity.. Lung cancer was the most common type of tumor included in the study (26 cases) followed by head and neck squamous cell carcinomas (three cases), and squamous cell carcinoma of the skin (two cases); other miscellaneous solid tumors were also represented. Toxicities included cheilitis, skin reactions, headache, and nausea and vomiting, as well as transient elevations of liver enzymes and triglyceride levels. Skin toxicities, consisting of erythema with desquamation and paronychia, were considered to be the dose-limiting toxicity, and were observed in two of six patients who received 175 mg/m2/d, and in two of five patients who received 200 mg/m2/d. Of the 30 patients with assessable lesions, response was evaluated in 26 patients and no major objective tumor response was observed. Two patients were able to receive the drug for longer than 1 year without significant toxicities. There was considerable variation in individual patients' peak plasma all-trans-RA levels, and a decrease in the area under the curve of all-trans-RA plasma concentration was observed in all four patients evaluated.. For phase II study of adult patients, we recommend 150 mg/m2 of all-trans-RA administered orally once a day. However, for better optimization of drug administration schedules, further studies are needed.

Topics: Adult; Aged; Alkaline Phosphatase; Cheilitis; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Female; Headache; Hearing Disorders; Humans; Liver; Liver Diseases; Male; Middle Aged; Nausea; Neoplasms; Skin Diseases; Tretinoin; Vomiting

Smith-Magenis syndrome (SMS, OMIM# 182290) is a rare congenital disorder which characterized by multiple abnormalities involving in craniofacial, skeletal, otorhinolaryngolocial, neurological, behavioral and others. 17p11.2 microdeletion and RAI1 mutations have been proven to be genetic lesions of this disease. However, the relationship between RAI1 variants and different phenotypes is still unclear. The discoveries of more RAI1 mutations in patients with different phenotypes will help to elucidate the pathogenesis of the RAI1 gene. Here, we describe a young patient with schizophrenia and headache as the main clinical presentation, with SMS-like features including depression, sleep disturbance and pain-free status. Whole exome sequencing and Sanger sequencing suggested that a de novo mutation (NM_030665.3: c.4256C > T/p.S1419F) of RAI1 may be the genetic lesion of the patient. The bioinformatic program predicted that the new mutation (p.S1419F), located in an evolutionarily conserved site of RAI1, was deleterious. Further, western blot analysis suggested that the novel mutation may decrease the protein levels of RAI1 in the patient. Hence, we reported a novel mutation of RAI1 in a patient with SMS, schizophrenia and headache. Our study may expand the spectrum of RAI1 mutations which may further contribute to the mechanisms underlying SMS, schizophrenia and headache.

Topics: Headache; Humans; Mutation; Phenotype; Schizophrenia; Smith-Magenis Syndrome; Trans-Activators; Transcription Factors; Tretinoin

For patients who have acute promyelocytic leukemia (APL) in second complete remission (CR2), optimal postremission strategies remain undefined.. The role of an oral arsenic trioxide (As. Seventy-three patients with APL in first relapse (R1) were studied. Oral As. For patients with relapsed APL, As

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Ascorbic Acid; Chemical and Drug Induced Liver Injury; Combined Modality Therapy; Disease-Free Survival; Female; Headache; Hematopoietic Stem Cell Transplantation; Hong Kong; Humans; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Remission Induction; Risk Factors; Severity of Illness Index; Survival Analysis; Time Factors; Transplantation, Autologous; Tretinoin; Young Adult

Alitretinoin is approved for the treatment of adults with severe chronic hand eczema (CHE) refractory to potent topical steroids. In the 6 years since launch, approximately 250 000 patients have been treated with alitretinoin.. To compare the postmarketing safety surveillance experience of alitretinoin with data from clinical trials and key safety issues with other retinoids.. An integrated safety analysis of the pivotal studies of alitretinoin and postmarketing adverse event (AE) reports received since approval for alitretinoin were analyzed.. In the pivotal trials, headache, erythema, nausea, increased blood triglycerides and increased blood creatinine phosphokinase were the most frequently reported AEs. Headache, hyperlipidemia and nausea were also frequently reported postmarketing AEs, but depression was relatively more frequently reported than in the pivotal trials. Inflammatory bowel disease and benign intracranial hypertension were rare, and very few cases have been reported in postmarketing surveillance. There have been no reports of teratogenicity in humans consequent to fetal exposure.. Safety data collected in pivotal trials and postmarketing surveillance suggest that alitretinoin is well tolerated by patients with CHE with a relatively low incidence of serious reactions. The adverse reaction profile is congruent with reported effects of other marketed oral retinoids.

Topics: Adult; Alitretinoin; Chronic Disease; Eczema; Female; Hand Dermatoses; Headache; Humans; Pregnancy; Tretinoin

Topics: Adult; Alitretinoin; Dermatologic Agents; Eczema; Follow-Up Studies; Hand Dermatoses; Headache; Humans; Male; Time Factors; Tretinoin

Topics: Acetazolamide; Adult; Antineoplastic Agents; Headache; Humans; Leukemia, Promyelocytic, Acute; Male; Tretinoin

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) and is rare in children (< 10% of childhood AML). It tends to bleed with disseminated intravascular coagulation (DIC) and intracranial hemorrhage complication is often fatal. We report a 12-year-old child with APL who suffered a subdural hemorrhage and initially presented with a subtle headache mistaken as the side effect of all-trans-retinoic acid (ATRA). Blood component therapy and a pediatric dosage of ATRA (25 mg/m2/day) combined with idarubicin as induction chemotherapy were administered in the first week, but the bleeding diathesis persisted and DIC profiles showed no improvement. The patient then developed photophobia, neck stiffness, and constant headache. Evidence of increased intracranial pressure (IICP) and persistent bleeding from previous venous puncture sites were also noticed clinically. DIC and life-threatening IICP were beyond control until the ATRA dosage was increased to adult levels (45 mg/m2/day). This case suggests that the ATRA dosage for pediatric APL patients must be modified according to clinical condition. Emergency brain imaging should be considered in APL patients with signs of IICP to distinguish intracranial lesions from ATRA complications.

Topics: Child; Disseminated Intravascular Coagulation; Headache; Hematoma, Subdural; Humans; Leukemia, Promyelocytic, Acute; Male; Partial Thromboplastin Time; Prothrombin Time; Tretinoin

An exploratory trial was conducted to evaluate toxicity and potential therapeutic role of all trans-retinoic acid (ATRA) given long-term together with chemotherapy and G-CSF to adult patients with acute myelogenous leukemia (AML).. ATRA was administered orally at 45 mg/m(2)/day on days 1-14 and 25 mg/m(2)/day on days 15-28 of two standard cycles (idarubicin, etoposide, cytarabine, G-CSF) and of up to three high-dose courses (cytarabine, G-CSF). The results obtained in 19 patients enrolled in the ATRA trial were compared with those from 29 comparable cases treated with the same schedule without ATRA, according to patient risk class and an in vitro study.. ATRA was administered for a median of 52 days to the patients selected for study who achieved a remission. ATRA-related toxicity was mostly non-severe apart from high incidence of headache in conjunction with high-dose cytarabine. Complete remission (CR) rate after cycle 1 (54%), kinetics of hematological recovery, postremission treatment realization, disease-free survival (DFS 37.5% at three years) and overall survival (30% at three years) were not different between ATRA-treated and untreated patients. The only significant prognostic factor was the patient risk class, as defined by cytogenetics and other clinical criteria: DFS rate was 57% at three years in standard-risk cases compared to only 19% in the high-risk group, with no influx by ATRA in either category. The in vitro study, in patients with a definite clinical response, failed to document any inhibitory or pro-apoptotic effect of ATRA on AML blast cells.. As a consequence to these results, the pilot ATRA phase was closed. This study does not suggest a significant role for the present ATRA schedule as an adjunct to standard antileukemic therapy in adult AML.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cytarabine; Disease-Free Survival; Etoposide; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Headache; Humans; Idarubicin; Leukemia, Myeloid; Life Tables; Male; Middle Aged; Neoplastic Stem Cells; Patient Compliance; Pilot Projects; Recombinant Proteins; Remission Induction; Survival Analysis; Treatment Failure; Tretinoin

Topics: Antineoplastic Agents; Child; Diagnosis, Differential; Diphosphonates; Headache; Humans; Hypercalcemia; Leukemia, Promyelocytic, Acute; Male; Nausea; Remission Induction; Time Factors; Tretinoin

Topics: Antineoplastic Agents; Child; Diplopia; Female; Headache; Humans; Leukemia, Promyelocytic, Acute; Paralysis; Pseudotumor Cerebri; Tretinoin; Trochlear Nerve Diseases

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Headache; Humans; Leukemia, Myeloid, Acute; Male; Stereoisomerism; Tretinoin

Only mild symptoms of retinoid intoxication--headache, hallucinations and vertebral pain--were observed after ingestion of 800 mg isotretinoin among other drugs. Transaminases and serum lipids were found within normal range five days later. Mucocutaneous effects due to overdosage were absent.

Topics: Adolescent; Hallucinations; Headache; Humans; Isotretinoin; Male; Suicide, Attempted; Tretinoin

Topics: Adult; Drug Administration Schedule; Female; Headache; Humans; Isotretinoin; Male; Menstruation Disturbances; Middle Aged; Neoplasms; Pain; Risk; Tretinoin

Topics: Administration, Oral; Aged; Epidermis; Etretinate; Female; Headache; Humans; Keratosis; Microscopy, Electron; Tretinoin

We investigated the effect of the synthetic vitamin A derivative isotretinoin (13-cis-retinoic acid) on advanced cancers in 103 patients and on preneoplastic lesions in five patients. Six of 14 patients with squamous cell epithelial cancers had objective regressions of skin or subcutaneous metastases. Three of five patients with preneoplastic lesions had objective responses. The major dose-limiting toxic effects were reversible dermatitis, emotional lability, and headaches. We conclude that the growth of some squamous cell epithelial malignancies can be inhibited by isotretinoin and suggest that other retinoids should be evaluated as antitumor agents.

Topics: Antineoplastic Agents; Carcinoma, Squamous Cell; Drug Eruptions; Drug Evaluation; Emotions; Headache; Humans; Isotretinoin; Neoplasms; Precancerous Conditions; Tretinoin

A phase I study of 13-cis-retinoic acid was done in 16 patients with head and neck malignancies using a modified Fibonacci search scheme, with individual doses ranging from 20 to 120 mg/m2. Drug doses greater than 60 mg/m2 induced intense headaches, urethritis, desquamative dermatitis, vertigo, and ataxia. The severity of these side effects precludes the use of 13-cis-retinoic acid as a potential chemopreventive agent at doses greater than 60 mg/m2.

Topics: Adult; Aged; Cheilitis; Dose-Response Relationship, Drug; Drug Evaluation; Female; Head and Neck Neoplasms; Headache; Humans; Ichthyosis; Isomerism; Male; Middle Aged; Tretinoin; Urethritis