melphalan and Erythema

Mucocutaneous involvement occurs predominantly in primary systemic amyloidosis as well as in myeloma-associated systemic amyloidosis. It is rarely observed in other types of amyloidoses. Signs of such involvement may aid in the early diagnosis of the disease process. Herein, we describe a 64-year-old white male patient with myeloma-associated systemic amyloidosis in whom the disease presented with unique cutaneous lesions consisting of chronic paronychia and palmodigital erythematous swelling and induration of the hands. Following weekly regimens with prednisone (20 mg/day) and melphalan (2 mg/day) administered every 16 weeks, almost complete resolution of the cutaneous lesions was observed after 1 year of therapy. Also, in response to chemotherapy, modest regression of the myelomatous bone lesions and complete resolution of the underlying gammopathy occurred.

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Chronic Disease; Drug Therapy, Combination; Erythema; Glucocorticoids; Hand Dermatoses; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Paronychia; Prednisone; Recurrence; Time Factors

Topics: Aged; Amyloidosis; Antineoplastic Agents; Bortezomib; Cyclophosphamide; Dexamethasone; Erythema; Female; Heart Failure; Humans; Melphalan; Monoclonal Gammopathy of Undetermined Significance

To determine whether the addition of high-dose tumour necrosis factor-alpha (TNF alpha) to isolated limb perfusion (ILP) with melphalan increases acute regional tissue toxicity compared to ILP with melphalan alone.. A retrospective, multivariate analysis of toxicity after normothermic (37--38 degrees C) and 'mild' hyperthermic (38--40 degrees C) ILPs for melanoma was undertaken. Normothermic ILP with melphalan was performed in 294 patients (70.8%), 'mild' hyperthermic ILP with melphalan in 71 patients (17.1%) and 'mild' hyperthermic ILP with melphalan combined with TNF alpha in 50 patients (12.0%). Toxicity was nil or mild (grades I--II according to Wieberdink et al.) in 339 patients (81.7%), and more severe acute regional toxicity (grades III--V) developed in 76 patients (18.3%). A stepwise logistic regression procedure was performed for the multivariate analysis of prognostic factors for more severe toxicity.. On univariate analysis, 'mild' hyperthermic ILP with melphalan plus TNF alpha significantly increased the incidence of more severe acute regional toxicity compared to normothermic and 'mild' hyperthermic ILP with melphalan alone (36% vs 16% and 17%; P=0.0038). However, after ILP using TNF alpha no grade IV (compartment compression syndrome) or grade V (toxicity necessitating amputation) reactions were seen. Significantly more severe toxicity was seen after ILPs performed between 1991 and 1994 compared with earlier ILPs (33%vs 14%P=0.0001). Also, women had a higher risk of more severe toxicity than men (22% vs 7%; P=0.0007). After multivariate analysis, prognostic factors which remained significant were: sex (P=0.0013) and either ILP schedule (P=0.013) or treatment period (P=0.0003).. Regional toxicity after 'mild' hyperthermic ILP with melphalan and TNF alpha was significantly increased compared to ILP with melphalan alone. This may be caused by increased thermal enhancement of melphalan due to the higher tissue temperatures (39--40 degrees C) at which the melphalan in the TNF alpha-ILPs was administered or by an interaction between high-dose TNF alpha and melphalan.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Blister; Chemotherapy, Cancer, Regional Perfusion; Compartment Syndromes; Edema; Erythema; Extremities; Female; Humans; Hyperthermia, Induced; Male; Melanoma; Melphalan; Middle Aged; Multivariate Analysis; Retrospective Studies; Severity of Illness Index; Sex Factors; Skin Neoplasms; Treatment Outcome; Tumor Necrosis Factor-alpha

The optimal toxic reaction of the normal tissues in perfused limbs after isolated limb perfusion (ILP) is unknown. Theoretically, more severe limb toxicity could reflect a concomitant increased toxic effect to the tumor and improved outcomes. We determined whether there is a relation between limb toxicity and treatment outcomes after ILP for recurrent limb melanoma.. Among 252 patients with recurrent melanoma of the limbs, treatment outcomes in 192 patients (76%) with no or mild acute limb toxicity were compared with those in 60 (24%) with more severe reactions. Multivariate analysis was used to identify prognostic factors for complete response, limb recurrence-free interval, and survival.. Among 112 patients with measurable disease, 65 patients (58%) had a complete response and 27 (42%) experienced a relapse in the perfused limb. For complete response, uninvolved regional lymph nodes (p = 0.0025) and ILP using tumor necrosis factor-alpha (p = 0.0076) appeared to be favorable prognostic factors in multivariate analysis. There was no evidence of a relation between limb toxicity and complete response either in univariate (p = 0.16) or multivariate analysis (p = 0.46). For limb recurrent-free interval, only the number of lesions was a significant prognostic factor (p = 0.047); limb toxicity was not (p = 0.095). In 140 patients with recurrent melanoma excised before or at the moment of ILP, independent prognostic factors for survival were gender, the number of positive nodes, and stage of disease. There was no relation between limb toxicity and survival in either univariate (p = 0.53) or multivariate analysis (p = 0.94). Forty-eight (34%) of the 140 patients had a relapse in the perfused limb. No prognostic factors for limb recurrent-free interval could be identified; limb toxicity was not related to relapse time in univariate or multivariate analyses (p = 0.16 and p = 0.14, respectively).. More severe acute limb toxicity is not associated with improved outcomes. One should aim at grade II toxicity (slight erythema or edema, compatible with complete recovery) at the most to increase the therapeutic ratio of ILP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Edema; Erythema; Extremities; Female; Humans; Hyperthermia, Induced; Interferon-gamma; Male; Melanoma; Melphalan; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Skin Neoplasms; Survival Rate; Treatment Outcome; Tumor Necrosis Factor-alpha

This paper reports clinical results of hyperthermal (41.5 degrees C) isolated perfusion of the lower limb for melanoma treatments in association with cytostatic drugs (L-PAM) in 10 consecutive patients. Attention is focussed on the toxicity effects in the search for a possible correlation between the treatment variables and toxicity. Careful heat administration techniques and thorough and accurate temperature monitoring have resulted in a uniform and closely controlled temperature distribution, allowing us to approach the limiting temperature value for possible damage both of the limb tissues and of the perfusate. Care was taken to avoid perfusate overheating (42 degrees C maximum). Local toxicity was observed between grades II and III. Systemic toxicity was of insignificant level. The clinical results show that high-temperature treatments with simultaneous administration of the cytostatic are feasible with acceptable toxicity. Further clinical investigations are recommended to ascertain the efficacy of the method.

Topics: Antineoplastic Agents, Alkylating; Blood Cell Count; Chemotherapy, Cancer, Regional Perfusion; Edema; Erythema; Female; Humans; Hyperthermia, Induced; Kidney; Leg; Liver; Male; Melanoma; Melphalan; Middle Aged; Temperature

Incidence, nature and cause of severe acute regional toxicity were studied in 181 patients who underwent normothermic (37-38 degrees C) or 'mild' hyperthermic (38-40 degrees C) isolated limb perfusion (ILP) with melphalan. The known risk factors for toxicity (sex, tissue temperature, blood gas values, isolation level and melphalan peak concentration) were analysed. Severe acute regional toxicity occurred in 30 patients (16%). The limb was painful, swollen, red and warm in 19, often with a smooth and glistening aspect. Blistering scattered over the extremity was seen in 11 cases. In another 11 patients, late blistering limited to the footsole or handpalm developed. Twenty-six patients with severe toxicity had undergone ILP at the iliac isolation level (p < 0.05). Sex and tissue temperature did not predict toxicity. Venous perfusate blood gas values were severely deteriorated in four patients; high calculated melphalan peak concentrations occurred in nine patients. Irreversible long-term morbidity as a sequence of severe toxicity occurred in 10 of the 30 patients. Only one of the 11 patients with late blisters limited to sole or palm developed long-term morbidity (p < 0.05). Thus, the only risk factor for severe acute regional toxicity that could be identified was iliac isolation level. However, in 27 of the 30 patients two or more risk factors were found.

Topics: Adult; Aged; Aged, 80 and over; Blister; Blood Gas Analysis; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Edema; Erythema; Extremities; Female; Humans; Hyperthermia, Induced; Incidence; Male; Melanoma; Melphalan; Middle Aged; Retrospective Studies; Risk Factors; Skin Neoplasms; Skin Temperature

Early skin reactions on mouse feet and delay in growth of a mouse tumor (CA NT) were measured after combined treatments with X-rays and the cytotoxic drug Melphalan. The drug was given as a single dose (10 mg kg-1) with graded single doses of X-rays, either before or after irradiation with an interval of up to 4 days. In the mouse skin, addition of the drug increased the radiation response only slightly. The maximum Enhancement Ratio (ER) measured at a skin reaction of 1.5 (approximately 23 Gy) was 1.07 +/- 0.02 SEM for the schedule MEL 3 days before X-rays. ER's for all schedules tested were similar with a range of 1.00 to 1.07. For the tumor more enhancement was observed; the largest ER's were found when Melphalan was given before rather than after irradiation, with maximum ER's of 2.3 and 2.4 when the drug was given 3 days or 1 day before X-rays. This has been attributed to reoxygenation of hypoxic cells after drug treatment, rendering the tumor more radiosensitive. The range of ER over all schedules was 1.5-2.4. Since ER is greater for the tumor than skin for all schedules, a therapeutic advantage is indicated under these specific experimental conditions of single X-ray and drug doses.

Topics: Animals; Combined Modality Therapy; Dose-Response Relationship, Radiation; Erythema; Foot Dermatoses; Male; Melphalan; Mice; Mice, Inbred CBA; Mice, Inbred Strains; Neoplasms, Experimental; Radiation Injuries, Experimental; Radiation-Sensitizing Agents; Skin; Time Factors