Long term use of thalidomide: safe and effective.

PURPOSE: To assess the efficacy and safety of high dose thalidomide therapy for longer duration of time in relapsed or refractory Multiple Myeloma (MM) patients. MATERIALS AND METHODS: Twelve relapsed/refractory MM patients (7 Males, 5 Females), who received thalidomide for more than 2 years were selected from the Out Patient Department of Institute Rotary Cancer Hospital (IRCH), AIIMS, India. Patients received thalidomide beginning at a dose of 200 mg/day with fortnightly increment to a maximum dose of 800 mg/day. Patients were assessed for response on the basis of M proteins (MP), bone marrow biopsy with touch preparation and skeletal X-rays. RESULTS: Nine patients tolerated a maximum dose of 800 mg/day whereas three patients were given 600 mg/day. All patients showed > or = 25-50% decline in serum /urine M proteins. Complete response/ near complete response was seen in 50%, partial response in 17% and minimal response (SD) in 34% patients. Median duration of thalidomide therapy was 47 months (range 29-60 months). Currently 11 patients are alive. TOXICITY: Varying degree of constipation and sedation were seen universally. One patient had DVT, which responded to anti-coagulant therapy. Other toxic effects included infections, skin reactions. There was no toxic death. CONCLUSION: Long-term use of thalidomide is safe, effective and feasible. We feel that this is one of few reports describing safety and efficacy of long-term thalidomide in relapsed and refractory MM.

Use of simple hematological, biochemical and clinical parameters to monitor response of multiple myeloma patients on high dose thalidomide therapy.

BACKGROUND: Evidence of increased bone marrow vascularity in multiple myeloma (MM) has led to the use of anti-angiogenic drugs especially thalidomide in relapsed or refractory patients. Currently, parameters such as serum/ urine electrophoresis for M (monoclonal) proteins, bone marrow biopsy with touch preparation and b2 microglobulin are routinely used to assess response to therapy. These investigations are expensive, invasive and require high technical setup. AIM: To correlate simple and routine hematological and biochemical parameters with the key marker of disease i.e. M proteins. SETTINGS AND DESIGN: This is an open label, uncontrolled, single-arm study. MATERIALS AND METHODS: Twenty nine refractory or relapsed multiple myeloma patients of both sexes (M=20, F=9) with age ranging between 35-72 years were initiated on 200 mg/day of thalidomide with fortnightly increments of 200 mg to a maximum tolerated dose not exceeding 800 mg/day. All hematological and biochemical parameters were monitored at monthly intervals for one year. STATISTICAL ANALYSIS: Correlation analysis was performed between hemoglobin (Hb), total leukocyte count (TLC), absolute neutrophil count (ANC), platelet count (PC), total proteins (TP), serum albumin and serum globulin on one hand and M protein levels on the other using Pearsons Correlation test by SPSS version 7.5. RESULT: Hb, TLC, ANC, PC and serum albumin levels showed a significant negative correlation with M proteins. A highly significant positive correlation existed between M proteins on one hand and TP and globulin levels on the other. Dryness of skin indicated positive response to therapy. These correlations were found to be significant at the end of one month of therapy in all the above-mentioned parameters except in TLC where it was significant after 2 months of thalidomide therapy. CONCLUSION: Results suggest that sustained efficacy of thalidomide therapy may be amenable to monitoring by these simple, inexpensive and easily available investigations after ascertaining an initial response by M protein and marrow plasmacytosis as these parameters closely follow M protein levels. However more studies are required to further substantiate these findings.

Anthelmintics: a review.

Helminths infect 25% of the world's population. In the last 50 years specific, safe and effective anthelminitic drug therapy for various parasitic infestations have been developed. The population of the developing countries across the globe suffers not only as a direct result of these infections but due also to co-morbidity such as anemia, malnutrition and reduced immunity status. Earlier anthelmintic drugs suffered from serious drawbacks such as hepatotoxicity and required specific preparation of the patient before treatment such as 12-hour fasting and pre-post purging caused considerable inconvenience to the patient. However, successive discoveries were born out of rationale approach that contributed to the effective, more specific and more easily tolerated drugs i.e. benzimidazoles, piperazine derivatives, avermectins, pyrazinoquinoline, etc. The present approach is to identify the causative parasite on the basis of stool examination and as a result of this approach, different drugs are prescribed for different parasitic infections. Examples include thiabendazole for cutaneous larva migrans, mebendazole for ascariasis, trichiuriasis and hookworm, albendazole for inoperable cases of cystic hydatid disease, DEC for Toxocara induced visceral larva migrans and loiasis, ivermectin for onchocerciasis, praziquantel for schistosomiasis and niridazole for Dracunculus medinensis. The cure rates with these drugs is also high e.g. thiabendazole produces a cure-rate of 98% in cutaneous larva migrans while mebendazole gives cure rate of 76-95% in ascariasis, trichiuriasis and hookworm infestations. A cure rate of 96% is produced by praziquantel in schistosomiasis. Most of these drugs have broad-spectrum anthelmentic effect. The present review aims at evaluating the currently available anthelmintics with respect to their efficacy and adverse effects. Steps to prevent impending helminthic drug resistance are also discussed.