James F. Conroy

Low dose bleomycin and methotrexate in cervical cancer.

Twenty patients with recurrent and disseminated carcinoma of the cervix were treated with Bleomycin, 10 mg/m2 weekly and Methotrexate, 10 mg/m2 every fourth day. Twelve of the 20 (60%) had a greater than 50% shrinking of measured tumor masses lasting a median remission time of 7.5 months. The data suggest that combination protracted chemotherapy with these drugs of metastatic cervical cancer might improve the outlook of patients with this condition.

Myeloproliferative disorders: II CML: Clonal evolution and its role in management

Abstract Twenty-three patients with an established diagnosis of Ph 1 positive chronic myelogenous leukemia have been entered into an experimental study to determine the effect on survival of splenectomy and intensive cycle-active chemotherapy based on serial cytogenetic monitoring. Initially, all patients were induced into hematologic remission with busulfan, splenectomized and treated with cytosine arabinoside and 6-thioguanine. Chemotherapy was modified or intensified when abnormal chromosomal patterns were observed in dividing bone marrow cells or non-stimulated short term blood cultures. Elimination or reduction of the abnormal clones was correlated with improved clinical status in the experimental group. Most of the patients who developed abnormal clones prior to clinical evidence of transformation either lost the clone or showed a marked reduction in the size of the clone after aggressive therapy was instituted. The results suggest that survival was prolonged in this group of patients (4–133 months) when compared to historical controls. Pre-selection of patients in the series does not appear to explain the data since 20 of the 23 patients presented with at least one of the poor prognostic factors described by Jacquillat et al. [28] and over 60% of them had two or more of the unfavorable signs at diagnosis.

Cancer of the esophagus following allogeneic bone marrow transplantation for acute leukemia.

The successful development of allogeneic bone marrow transplantation (BMT) has markedly improved the treatment results for acute leukemia and other hematologic diseases. However, significant complications arc associated with this procedure including the development of chronic graft versus host disease (GVHD). Treatment for this condition requires chronic immunosuppression which can lead to the development of second cancers. It is well known that immunosuppression is associated with a variety of tumors, most commonly lymphoma. The development of solid tumors appears to be less common but follow-up studies of patients treated for Hodgkins disease demonstrate a rising incidence of solid tumor development after a delay of 5 to 10 years.We describe a patient recently treated for a squamous cell carcinoma of the esophagus which developed 5 years after an allogeneic BMT for acute myclogenous leukemia (AML). The patient had been treated with immunosuppressants for chronic GVHD. The clinical course is described and the literature is reviewed regarding recent experience with the development of solid tumors following allogeneic BMT.The majority of second tumors following BMT are lymphomas and leukemias. Secondary solid tumors are less common, but the incidence appears to increase over time. Squamous carcinomas are most common and a preparative regimen combining radiation and chemotherapy may increase risk.Careful long-term follow-up of BMT is essential in order to detect second tumors at an early stage.

4'-(9-acridinylamino)methane-sulfon-m-anisidide (m-AMSA) and 5-azacytidine (AZA) in the treatment of relapsed adult acute leukemia.

BETWEEN MARCH 1980 AND DECEMBER 1981, 22 patients were treated with 4‘(9-acridinylamino)methanesulfon--anisidide (AMSA) and 5-azacytidine (AZA), each given by I. V. push in a dosage of 150 mg/m2 for 5 days. Seven of 12 prior-remitting, acute nonlymphoblastic leukemia (ANLL) patients achieved complete remission (58%). Six ANLL patients who failed to remit on standard daunorubicin-cytosine arabinoside programs also failed to remit on the m-AMSA-AZA combination. Two patients with relapsed acute lymphatic leukemia (ALL) also failed while two patients with chronic myelocytic leukemia (CML) in evolution were cytoreduced.The seven patients who achieved remission had additional relapse-free survival for a median of six months (range 1–23+ months). One patient obtained a second remission with m-AMSA-AZA after relapse which followed a 9-month period of nonmaintained remission.Most patients demonstrated mild to moderate nausea and vomiting. Hepatic toxicity was mild to infrequent. Only four patients showed cardiac toxicity which was not life-threatening. The most troublesome toxicity was mucositis and was seen in 11 patients; four whom required I. V. hyperalimentation.We conclude that this combination is an effective salvage program for relapsed prior-remitting ANLL Future studies should be conducted in three areas. The first study might be a comparison of relapsed prior-remitting ANLL with single-agent m-AMSA. The second, in untreated ANLL, following induction with DAT, might use m-AMSA-AZA in consolidation and maintenance arms of future protocols. The final study should explore m-AMSA-AZA activity in evolved CML in a greater number of patients.

ICRF-159 (razoxane) in patients with advanced squamous cell carcinoma of the uterine cervix: For the gynecologic oncology group

THIRTY-ONE PATIENTS WITH ADVANCED SQUAMOUS cell carcinoma of the cervix were entered onto this phase II study evaluating the efficacy of ICRF-159 (razoxane). Three of these patients were excluded; one had no tumor, one had a second primary, and one received no therapy.ICRF-159 was administered orally at a dose of 2.5 g/m2 weekly until progression, unacceptable toxicity, or death. Adverse effects were primarily hematologie in nature. Twenty-three of the 28 patients exhibited leukopenia which in ten instances was severe (below 2000/mm3). Seven cases had thrombocytopenia (one case below 50,000/mm3). Other toxicity, including fever and anorexia, was mild to moderate. There was tumor response in five (18%) patients (one CR, four PRs) ranging from 1 to 5 months. Fifteen patients with stable disease and eight with progressive disease had a median survival duration of 3.8+ and 3.5+ months, respectively.ICRF-159 showed limited activity in this patient population. However, it might be considered for combination with other low myelosuppressive agents.

An unusual extramedullary relapse of acute nonlymphocytic leukemia after allogeneic bone marrow transplantation

Recurrent leukemia following allogeneic hone marrow transplantation (BMT) for acute nonlymphocytic leukemia (ANLL.) continues to he a cause of morbidity and mortality. Most relapses occur within the first 6–12 months, although disease-free survival curves do not hegin to plateau until 24 months posttransplant. The majority of relapses occur in the hone marrow. Extramedullary relapses usually occur in “sequestered sites,” i.e., the testis and central nervous system. Although the true incidence of extramedullary relapse in “nonsequestered” sites after allogeneic BMT for ANLL is unknown, it appears that this type of relapse is distinctly unusual. The authors present a case of an unusual extra- medullary relapse of ANLL in the breast at day + 613 after allogeneic BMT for AMLL. In addition, we briefly review the Hnglish BMT literature and discuss the differential diagnosis of breast masses in women who survive allogeneic BMT for ANLL.

Efficacy of Dacarbazine Imidazole Carboxamide and Mitomycin C Combination Therapy in Patients with Adenocarcinoma of the Colon Refractory to 5-Fluorouracil Therapy

Therapy for metastatic cancer of the colon is a major problem for the medical oncologist. This tumor is refractory to most chemotherapeutic maneuvers. Moertel has noted that the median survival in this group is only 7 months, with a median survival of 5 months in patients with liver metastasis [13]. 5-Fluorouracil (5-FU), the standard agent for this disease, has a response rate of 20% at best [3], and the response rate falls to 10% if stringent criteria for hepatic response are applied [4]. combinations.

Malignant paraganglioma of retroperitoneum light, electron microscopic and ultrasonographic study

A malignant retroperitoneal nonchromaffin paraganglioma in a thirty-four-year-old man was studied by light and electron microscopy. Histologically, the tumor cells displayed a tendency to surround granular, eosinophilic intercellular material and to form nests and pseudo-acini. Ultrastructurally, the tumor was composed of moderately well-differentiated epithelial cells intermixed with sparse sustentacular cells. An organoid pattern, reminiscent of the functional anatomic unit of nonchromaffin paraganglia, was seen occasionally. Epithelial cells formed pseudo-acini around dilated microvillous processes. These morphologic features are consistent with the neurocrestal origin of paragangliomas. The patient died ten months after presentation despite an initial favorable response to irradiation.

High-dose cytosine arabinoside and etoposide in the treatment of relapsed or refractory adult leukemia.

Thirteen patients with leukemia were treated with a combination of cytosine arabinoside (ara-C) (3 g/m2 by 1-h infusion every 12 h for 12 doses) and etoposide (100 mg/m2 daily over 1 h for 3 doses). Toxicity of the regimen consisted of severe hematologic suppression, moderate abdominal colic with vomiting and diarrhea, and occasionally severe central nervous system (CNS) toxicity. Two patients received the regimen as consolidation for acute myelogenous leukemia in remission. Of the remaining 11 patients with chronic myeloid leukemia (CML)-blast crises or relapsed/refractory acute myeloid leukemia (AML), nine patients (82%) obtained CR (or chronic phase) and two patients obtained partial remission (PR). High-dose ara-C and etoposide is an effective but toxic regimen for the treatment of relapsed or refractory myeloid leukemias.

Dibromodulcitol in the treatment of metastatic hemangiopericytoma

HEMANGIOPERICYTOMA is an uncommon sarcoma arising from the pericapillary cells. While the rarity of this lesion precludes randomized investigation, metastatic hemangiopericytoma has been noted to respond to a variety of agents, including vincristine, adriamycin, actinomycin, and high-dose methotrexate. We wish to report an unusual case of this disease which failed to respond to the above but then exhibited a marked response to dibromodulcitol. In light of the unusual nature of this response, we would like to suggest a controlled trial of the use of dibromodulcitol in patients with this rare tumor.Dibromodulcitol was administered to a 68-year-old female with metastatic hemangiopericytoma. While this tumor had failed to respond to several other cytotoxic regimens, marked tumor regression lasting for greater than 20 months occurred on an intermittent schedule of 300 mg daily for 7 days repeated on a 28 day cycle. It is impossible to determine the response rate in a single patient and this agent was not effective in patients reported by the E.C.O.G.1 While dibromodulcitol should probably not be used as the first agent in patients with hemangiopericytoma, therapy with this drug is warranted when patients fail to respond to initial chemotherapy.