Mechlorethamine Research Articles

Splenectomy, Chemotherapy, and Survival in Hodgkin Disease

The question was raised whether routine splenectomy might, by virtue of its effects on the receipt of subsequent chemotherapy, offer long-term benefits to patients with advanced Hodgkin disease. Therefore, we compared followup data from a group of patients who were receiving mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone (MOPP regimen) and who had had splenectomies to a group of similarly treated, carefully matched control patients on the MOPP regimen who had not had splenectomies. Our results indicate no important difference in duration of survival or long-term remission status. There was only a suggestion that splenectomy in such patients may be followed by impaired resistance to subsequent infections. Therefore, although early splenectomy can be important in the assessment of splenic disease, it must not be considered to be a therapeutic procedure per se.

A New Combination Chemotherapy for Resistant Hodgkin Disease

A new four-drug combination chemotherapeutic regimen (BVDS) was used in the treatment of advanced Hodgkin disease resistant to MOPP (mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone). The BVDS regimen, consisting of 12 cycles of bleomycin sulfate, vinblastine sulfate, doxorubicin hydrochloride (Adriamycin), and streptozocin (streptozotocin), was administered to ten patients. Responses were seen in five (50%) of these patients. Complete remissions occurred in three (30%). These results suggest that BVDS is an effective alternative regimen to MOPP, and may be of benefit not only to patients resistant to MOPP, but also to newly-diagnosed patients with advanced hodgkin disease when combined sequentially with MOPP.

Intravenous Desensitization to Mechlorethamine in Patients With Psoriasis

Eight patients with psoriasis who had developed contact allergy to mechlorethamine hydrochloride (nitrogen mustard) were subjected to a regimen of intravenous infusion of small amounts of the drug in an attempt to produce desensitization. Although three of eight developed negative patch tests and were presumed to be desensitized, only one patient was able to use the drug therapeutically, and then only for a period of eight months, after which allergy recurred. The other two patients whose allergic contact dermatitis was abolished by the infusions were unable to use mechlorethamine therapeutically because of pruritus. Seven patients experienced some adverse reaction to the infusion. Intravenous desensitization of psoriatic patients who are allergic to mechlorethamine was not successful enough as a useful clinical procedure to allow them to once again use the drug therapeutically.

Intravenous desensitization to mechlorethamine in patients with psoriasis

Eight patients with psoriasis who had developed contact allergy to mechlorethamine hydrochloride (nitrogen mustard) were subjected to a regimen of intravenous infusion of small amounts of the drug in an attempt to produce desensitization. Although three of eight developed negative patch tests and were presumed to be desensitized, only one patient was able to use the drug therapeutically, and then only for a period of eight months, after which allergy recurred. The other two patients whose allergic contact dermatitis was abolished by the infusions were unable to use mechlorethamine therapeutically because of pruritus. Seven patients experienced some adverse reaction to the infusion. Intravenous desensitization of psoriatic patients who are allergic to mechlorethamine was not successful enough as a useful clinical procedure to allow them to once again use the drug therapeutically.

Treatment of Mycosis Fungoides With Topical Nitrosourea Compounds

Twenty-six patients with mycosis fungoides were treated topically with three nitrosourea compounds: carmustine (BCNU), lomustine (CCNU), and 1-methyl-1-nitrosourea. A high percentage experienced good to excellent results. Remissions following treatment of individual lesions varied from one month to at least three years. Remissions following total body surface treatment varied from two weeks to at least four months. Two of 13 patients treated over the entire body suffered temporary bone marrow depression, indluding one with severe pancytopenia. This toxic effect was attributed to lomustine and was not seen in patients treated with carmustine alone. Thirteen patients highly allergic to mechlorethamine hydrochloride showed no cross-sensitivity to nitrosourea compounds. A primary irritant dermatitis occurred in about one half of the patients and telangiectasia in two. Two patients developed hypersensitivity to nitrosourea compounds. Carmustine is the preferred nitrosourea compound for topical therapy of mycosis fungoides.

Mechlorethamine Desensitization in Therapy for Mycosis Fungoides

Five patients with mycosis fungoides who had developed contact dermatitis to a nitrogen mustard, mechlorethamine hydrochloride, even in low concentrations (1 to 5 mg/100 ml), received daily total-body applications of extremely dilute solutions (0.01 to 0.1 mg/100 ml) of mechlorethamine. The concentrations of the drug were approximately doubled weekly if the patient could tolerate it, or they were raised more slowly if the patient could not. Attempts to desensitize one patient were discontinued since he was unable to tolerate a greater concentration than 1.0 mg/100 ml after trying for one year. Another patient was able to tolerate a concentration of 3 mg/100 ml after three months, at which time his skin had completely cleared and treatment was stopped. Three other patients were desensitized during a period of 8 to 13 months to the point of tolerating the full therapeutic concentration used in our clinic (20 mg/100 ml) without experiencing dermatitis or pruritus.

Treatment of Pleural Mesothelium

To the Editor.— I was interested in the article by Strober et al, Malignant Pleural Disease: A Radiotherapeutic Approach to the Problem (226:296, 1973), that emphasized a simple, safe, and effective means of controlling malignant pleural disease. All of their patients had pleural disease as a result of metastases from another primary source, either lung or breast. May I comment briefly on another malignant pleural process that we treated recently with radiotherapy with equally satisfactory results. A 29-year-old man with an unexplained pleural effusion was ultimately found, by an open pleural biopsy (a previous needle biopsy was inconclusive), to have a diffuse malignant pleural mesothelioma. He had been subject to recurrent pleural effusions that had required multiple thoracenteses. There was no known exposure to asbestos. The therapy for this disease is not well established. Surgical excision has been replaced by intrapleural agents such as mechlorethamine hydrochloride and gold Au 198.

BCG Vaccination for Hodgkin Disease

To the Editor.— The statement attributed to me that we have been killing people with chemotherapy for so many years is partially out of context (228:28, 1974). There are very few hematologists today who have only practiced for the last decade who have actually seen a patient die of Hodgkin disease. However, Hodgkin disease patients do die, and usually of complications of therapy. Admittedly, this is a lesser number, thanks to current treatment schedules. Even so, this smaller number must receive our continued efforts, and to this end my paper was directed. The paper clearly outlines that I undertook to improve active cell-mediated immunity (CMI) by combining the specific and nonspecific effects of BCG vaccine along with transfer factor in a specific group of patients, namely those in whom the combined regimen of mechlorethamine hydrochloride, vincristine sulfate (Oncovin), procarbazine hydrochloride, and prednisone (MOPP) had failed. While some viable T cells might

Multiple Chemotherapeutic Agents for Hodgkin Disease

Two hundred forty-seven patients with disseminated Hodgkin disease were randomly treated with one of three intensive multiple-agent regimens. Partial or complete response rates of 90% were obtained with each routine. The "MOPP" regimen—mechlorethamine hydrochloride, vincristine sulfate (Oncovin), procarbazine hydrochloride, and prednisone—yielded the longest duration of response but also had the highest toxicity. There was no difference in survival rates among patients on the three routines. Major factors associated with good response were female sex and little or no prior therapy. Minor favorable factors were stage III disease, lack of systemic symptoms, former responsiveness to therapy, and age of less than 60 years. The simultaneous dosage routine was superior in both response rate and lessened toxicity compared to sequential usage of the same drugs with the same total dosage.

Urticaria and Anaphylactoid Reactions

A 68-year-old woman developed an urticarial and anaphylactoid reaction after total body surface application of mechlorethamine hydrochloride. Application of mechlorethamine to a test area produced a wheal and flare response and confirmed the diagnosis. This patient previously used this chemical intermittently over a five-year period without allergic manifestations. To our knowledge, this is the first documented anaphylactoid reaction to topical application of mechlorethamine. This report alerts physicians using mechlorethamine and other medicaments topically to the always potentially fatal complication of anaphylaxis.

Combined chemotherapy radiotherapy management of stage 3 Hodgkin's disease.

Thirty-three stage IIIAand IIIBpatients with Hodgkin's disease have been treated with a combination chemotherapy-radiotherapy program for the past five years. In this program, chemotherapy was administered prior to radiotherapy. The primary purpose for administering preliminary chemotherapy was to insure completion of a scheduled program of radiotherapy. A possible secondary advantage may be a reduction in the incidence of subsequent new disease. Initially, our drug regimen consisted of one course of cyclophosphamide and vincrinstine sulfate. When procarbazine hydrochloride became available, our chemotherapy program was changed to a combination of mechlorethamine hydrochloride, vincristine sulfate (Oncovin), procarbazine hydrochloride, and prednisone (MOPP). Two courses of MOPP were used initially; later the number of courses was changed to three. Survival figures for three and five years are 70% and 68%, respectively.

Chemotherapy of Hodgkin's Disease

A therapeutic regimen (MOPP) that consisted of a combination of mechlorethamine hydrochloride, 3 to 6 mg/sq m intravenously, days 1 and 8, vincristine sulfate, 0.7 or 1.4 mg/sq m intravenously, days 1 and 8, procarbazine hydrochloride, 50 or 100 mg/sq m orally, every day for ten days, and prednisone, 40 mg/sq m orally, every day for ten days, was given every four weeks for 24 weeks to 164 patients with disseminated Hodgkin's disease. Patients in complete remission then received either no therapy or MOPP therapy every eight weeks. One hundred six patients achieved a complete remission (65%). The remission rate for stages IIIA, IIIB, and IVA ranged between 78% and 82%; for IVB it was 56%. At 95 weeks, 78% of the patients receiving maintenance therapy and only 50% of those not receiving maintenance were still in complete remission.

Chemotherapy of Lymphoma With Mechlorethamine and Vinblastine

To determine the relative efficacy of mechlorethamine hydrochloride and vinblastine sulfate, 172 patients with Hodgkin's disease, lymphosarcoma, and reticulum cell sarcoma were randomly assigned to receive one or the other of these agents. If treatment with the first compound failed, each patient was to be treated with the second. No significant differences were found between the therapeutic results obtained with these two drugs in any of these illnesses. The Rye classification for Hodgkin's disease was not found to be of prognostic value for response to these agents. The patients with nodular, poorly differentiated lymphocytic lymphoma according to the Gall-Rappaport classification for non-Hodgkin's lymphoma, responded significantly better to mechlorethamine than to vinblastine, and their response rate with the alkylating agent was significantly higher than that of the other persons with non-Hodgkin's lymphoma.

Combination Therapy of Hodgkin's Disease

To the Editor.— Dr. William's criticism (222:486, 1972) of the recent article entitled Combination Chemotherapy of Hodgkin's Disease in Private Practice (221:261, 1972) is illconsidered. Much of medicine is complex, and the complexity of the MOPP therapy (mechlorethamine hydrochloride, vincristine sulfate, procarbazine hydrochloride, and prednisone) for Hodgkin's disease is no less complex when administered in the setting of the university hospital than when given at the community level. All therapy, whether given for malignant disease or not, must be administered by a physician well-versed in the pharmacology of the drugs he is using. To envelop medical oncology in an aura of hypersophistication is undesirable and does much to reinforce the uninformed medical practitioner's attitude that antineoplastic agents are poisons. I am quite confident that many more people die each year of digitalis intoxication than from antineoplastic agents. I am sure there are also many patients from whom cancer chemotherapy has been

Management With Combination Therapy

In original CURRENT CONCEPTS IN CANCER series on Hodgkin's Disease inThe Journalin 1965, Gellhorn 2 suggested that the objectives of therapeutic management in advanced Hodgkin's disease are to suppress symptomatic manifestations, anticipate or control complications, and provide support to sufferers of a debilitating disease. At that time, four classes of drugs were available for treatment of patients with stage III and IV disease; namely, alkylating agents, particularly mechlorethamine hydrochloride (nitrogen mustard), vinblastine sulfate (Velban), procarbazine hydrochloride (Natulan [Great Britain]; Matulane, comparable US product), and prednisone (Deltasone). Furthermore, he suggested sequential use of single agents from each class, an JAMA, Jan 8, 1973 • Vol 223, No 2 ticipating no cross resistance. Single agents in patients with stage III or IV disease produce tumor regressions 50% to 70% of time, but only 10% to 20% of patients achieve complete remissions. 3 In these patients,

Chemotherapy of Burkitt's Tumor at the University of Ibadan, Nigeria

Our work on the chemotherapy of Burkitt's tumor started in 1961 shortly after its recognition as a clinical entity. The management of Burkitt's tumor patients at the University College Hospital, Ibadan, has always been a team effort, with many colleagues in surgery, pediatrics, pathology and hematology participating, and this short report is submitted on their behalf as well. <h3>Cases Treated and Drugs Used</h3> In the past 11 years of the chemotherapy program over 500 patients with Burkitt's tumor have been seen. About 400 patients received some treatment. Various clinical trials were initiated on these cases. Alkylating agents, antibiotics, alkaloids, antimetabolites, and indeed any cytotoxic drug that could be obtained were included in the trial. Of these, the most effective drugs were cyclophosphamide (Cytoxan), mechlorethamine hydrochloride (nitrogen mustard), and methotrexate. <i>Cyclophosphamide</i>was given intravenously at a dose of 10-15 mg/kg of body weight daily for 7-10 days. When the tumor was

Combination Chemotherapy for Patients With Malignant Lymphoma

The development of effective combination chemotherapy for patients with malignant lymphoma was based on clinical experience in patients with acute leukemia developed at the National Cancer Institute, and specific baseline knowledge of the effects of single agents in patients with malignant lymphoma. In 1965 we reported the results of a controlled clinical trial in a large number of patients, observing the effects of a vinca alkaloid or cyclophosphamide on induction of response, complete response rate, cross resistance, and the effect of maintenance on remission duration. We also reported the usefulness of a new agent, procarbazine hydrochloride, that appeared to be effective in alkylating agent-resistant patients. These results indicated that a combination treatment program in stage III or IV cases with mechlorethamine hydrochloride (nitrogen mustard), vincristine, procarbazine, and prednisone (MOPP) would be ideal, since these drugs were individually effective and had different major clinical toxicities. Besides the concept of combining these

Complete Regressions of Mycosis Fungoides With Topical Mechlorethamine Hydrochloride

Survival of patients with mycosis fungoides, a lymphoma initially appearing in the skin and thereafter spreading to internal organs, has not been substantially improved by chemotherapeutic measures in use over the past two decades. In only a few instances has the disease been reported to undergo complete regression following therapy. In the past four years we have intensively treated more than 70 patients with topical mechlorethamine hydrochloride (nitrogen mustard) preparations, usually consisting of 10 mg of drug dissolved in 2 oz of water. These solutions have been applied to the entire body surface daily, or three times weekly, until disappearance of disease. Thereafter applications have been continued at less frequent intervals. In patients with disease limited to the skin, prior to lymph node involvement, complete regression of disease has been achieved and maintained in more than 50% of cases. Duration of therapy necessary to achieve complete disappearance of disease has

Complete regressions of mycosis fungoides with topical mechlorethamine hydrochloride.

Survival of patients with mycosis fungoides, a lymphoma initially appearing in the skin and thereafter spreading to internal organs, has not been substantially improved by chemotherapeutic measures in use over the past two decades. In only a few instances has the disease been reported to undergo complete regression following therapy. In the past four years we have intensively treated more than 70 patients with topical mechlorethamine hydrochloride (nitrogen mustard) preparations, usually consisting of 10 mg of drug dissolved in 2 oz of water. These solutions have been applied to the entire body surface daily, or three times weekly, until disappearance of disease. Thereafter applications have been continued at less frequent intervals. In patients with disease limited to the skin, prior to lymph node involvement, complete regression of disease has been achieved and maintained in more than 50% of cases. Duration of therapy necessary to achieve complete disappearance of disease has

Topical therapy of psoriasis with mechlorethamine

Aqueous solutions of mechlorethamine (Mustargen) hydrochloride (0.055 to 0.00625%) have been used in courses of seven to ten days on lesions of psoriasis in 42 patients. A significant involutionary effect was obtained with the 0.0125% to 0.05% concentrations, particularly on the trunk. The rate of contact sensitization ranged from 50% to more than 80%, and was highest with the 0.05% concentration. Occasional Koebner reactions and paradoxical results were noted. The high rate of sensitization precludes the use of this agent in the practical management of psoriasis.