Gordon B. Magill

Malignant schwannoma--clinical characteristics, survival, and response to therapy.

One hundred and sixty‐five cases of malignant schwannoma were reviewed. Sixty‐five (40%) of the patients had evidence of disseminated neurofibromatosis. Patients with neurofibromatosis were younger, had malignant schwannomas that were centrally rather than peripherally located, and had a shorter five‐year survival (23%) than patients with solitary malignant schwannomas (47%). Histologically, tumors developing in patients with neurofibromatosis had a collagenous appearance, while tumors in patients without neurofibromatosis were undifferentiated and highly cellular. The clinical course of both groups of patients tended to be that of multiple local recurrences, although local recurrence had a more ominous prognosis in patients with neurofibromatosis. Chemotherapy responses in all these patients were extremely poor; however, the results of adjuvant therapy after surgery appeared encouraging. Fourteen patients (8.5%) had a malignant schwannoma in an area of prior radiation therapy and died of disease a median of 14 months after diagnosis. Malignant schwannoma should be considered in the differential diagnosis of tumors developing in areas previously treated with radiation.

Malignant mesothelioma of the pleura: Review of 123 patients

One‐hundred‐twenty‐three cases of malignant pleural mesothelioma were reviewed. Exposure to asbestos or to other industrial dusts or chemicals was an important etiologic factor with 24% of patients relating such a history. A history of prior irradiation or previous lung disease was also occasionally noted. Diagnosis was most often made by exploratory thoracotomy, with pleural biopsy or cytology rarely helpful. Except for nine patients, tumor was confined to the chest at the time of diagnosis, but in 33 of the remaining 114 patients, spread to the abdomen or distant metastasis was seen during the course of disease. Surgery and radiotherapy were ineffective in preventing local recurrence. There were only three major responses to chemotherapy in 111 trials. Median survival was 12 months, and only seven patients (5.6%) lived more than five years. Patients with epithelial mesothelioma and Stage I disease had the most favorable prognosis.

Extraosseous osteogenic sarcoma: A review of 48 patients

The clinical records and histologic material of 48 patients with extraosseous osteogenic sarcoma were reviewed. Most patients developed their tumors in the fifth or sixth decades of life. Five patients (10%) developed neoplasms in an area of prior radiation therapy, a median of 15 years after their exposure. Six patients (13%) related a history of trauma to the area where their extraosseous osteogenic sarcoma developed. The course of most patients was that of multiple local recurrences (69%) followed by pulmonary metastases (80%) and death (76%). Amputation or wide resection followed by irradiation appeared to be the most effective types of therapy, with median survivals greater than 60 months for patients receiving these treatments, compared to 28 months for patients initially treated with resection alone. Chemotherapy was not effective for patients with advanced disease; however, adjuvant chemotherapy after surgery may have been of value. Four of five patients who received adjuvant chemotherapy after surgery are alive and disease‐free; the only two survivors after development of pulmonary metastases received adjuvant chemotherapy after surgical resection of visible pulmonary metastases.

A prospective randomized trial of adjuvant chemotherapy with bolus versus continuous infusion of doxorubicin in patients with high‐grade extremity soft tissue sarcoma and an analysis of prognostic factors

A prospective randomized trial was conducted to compare the cardiotoxic and therapeutic effects of doxorubicin (60 mg/m2 every 3 to 4 weeks) administered by bolus or 72‐hour continuous infusion as adjuvant chemotherapy in 82 eligible patients after resection of high‐grade soft tissue sarcoma of the extremity or superficial trunk. Cardiac toxicity, defined as a 10% or greater decrease in left ventricular ejection fraction as assessed by radionuclide cineangiography, was evaluated in 69 patients. Cardiotoxicity was seen in 61% of patients in the bolus treatment arm with the median doxorubicin dose of 420 mg/m2. Among patients who received continuous infusion, 42% had cardiotoxicity with a median dose of 540 mg/m2. The rate of cardiotoxicity as a function of the cumulative dose of doxorubicin was significantly higher in the bolus treatment arm (P = 0.0017). Two patients in each group had clinical congestive heart failure, with one cardiac death occurring in each. There was a trend toward a lower rate of metastasis (P = 0.19) and a significantly lower rate of death of disease (P = 0.036) for patients treated with the bolus dose. Cox model analysis identified three unfavorable characteristics for the rate of developing a distant metastasis: blood transfusion within 24 hours of operation (P < 0.00001), tumor deep to the fascia and 5 cm or more in size (P = 0.0043), and a histologic subtype other than liposarcoma (P = 0.0002). The unfavorable effect of continuous infusion was not selected in the model (P = 0.16). Adjuvant chemotherapy for patients with soft tissue sarcoma is investigational. Furthermore, the impact of perioperative blood transfusion merits further study.

Preoperative chemotherapy and radiation therapy in the management of anal epidermoid carcinoma

Management of epidermoid carcinoma of the anus has been primarily surgical in the past. Since it is a relatively rare entity, meaningful survival statistics are difficult to obtain. Five‐year survival rates fall between 35 and 68% in patients treated with surgery and/or radiotherapy. Based on preliminary studies indicating promising results with the use of mitomycin C and 5‐fluorouracil (5‐FU) chemotherapy combined preoperatively with radiation therapy, these authors initiated a protocol in 1973 utilizing this multimodality approach. The preoperative treatment consisted of mitomycin C 15 mg/m2 IV bolus on day 1 and 5‐FU 750 mg/m2/24 hours continuous infusion for five days. Radiation followed chemotherapy and consisted of 3000 rad given at 200 rad per day for 15 fractions. Of 37 patients entered on the protocol, 30 had primary disease and seven had been previously treated and had local recurrences. Median follow‐up has been 28 months (range, 5‐74 months). Of 31 patients with measurable lesions, 29 (94%) had major clinical responses (CR + PR) to the combined chemotherapy and radiation. Pathologic responses were also impressive with 53% (17/32) showing no evidence of residual tumor in the subsequently resected surgical specimen. Of the 37 patients treated, seven (19%) have had recurrences. The recurrence rate was 4/17 (24%) for those who had local excision following complete response to therapy as opposed to 3/18 (17%) for those treated by abdominoperineal resection. Thus it appears that the combination of preoperative mitomycin C and 5‐FU with radiotherapy is effective at least in significantly downstaging this uncommon malignancy. Its ultimate effect on recurrence rate and overall patient survival awaits longer follow‐up.

Chemotherapy of germ cell tumors of the testis. I. Induction of remissions with vinblastine, actinomycin D, and bleomycin

Patients with disseminated testicular carcinoma were treated with the combination of vinblastine, actinomycin D, and bleomycin in an attempt to induce remission. Of 47 patients receiving an initial adequate trial of this regimen, 34% achieved a complete or partial remission; in the 18 patients with either no prior nonsurgical treatment or treatment with actinomycin D alone, the response rate was 61%. Those who attained complete response status enjoyed significant prolongation of life compared with the nonresponders or partial responders. Responses were seen in all histologic categories and were not related to the performance status of the patient at the start of the trial, to the total dose of drug in the first month of therapy, or the extent of hematologic toxicity produced by the drugs. Responders had a higher incidence of stomatitis than nonresponders.

Microangiopathic hemolytic anemia observed after treatment of epidermoid carcinoma with mitomycin C and 5-fluorouracil

Two patients with epidermoid carcinoma treated with mitomycin‐C (Mit‐C) and 5‐fluorouracil (5‐FU) developed microangiopathic hemolytic anemia (MAHA), renal failure, and altered mental status. Patient 1 was free of metastatic disease, on maintenance Mit‐C and 5‐FU when MAHA changes appeared. Patient 2 had recurrent carcinoma in the pelvic area when MAHA changes appeared. In both patients, MAHA changes and neurologic function improved after exchange plasmapheresis. This is the first report of epidermoid carcinoma manifesting MAHA changes after chemotherapy. Speculation as to pathogenesis and appropriate therapy are discussed.

Combination Chemotherapy with cis-Diamminedichloroplatinum (II) and Bleomycin in Tumors of the Head and Neck

28 patients with head and neck tumors not suitable for definitive treatment with radiation or surgery were treated with cis-diamminedichloroplatinum (II) and bleomycin in combination. Of 24 adequately

Multidisciplinary preoperative approach to the management of epidermoid carcinoma of the anus and anorectum.

Summary and ConclusionAdministration of mitomycin C, 5-fluorouracil, and radiotherapy greatly reduced gross tumor sizes preoperatively in nine of ten patients who had epidermoid carcinoma of the anus and anorectum. In four of the cases there was no microscopic evidence of residual cancer in the resected specimens following this management and five specimens showed only histologic evidence of tumor. Because of these findings, we are encouraged to do more local excisions for cure whenever feasible, rather than doing abdominoperineal resection for this disease. Ultimately only accumulated time and continued experience will determine the efficacy of approach, in which preoperative multidisciplinary treatment is followed by more conservative surgical treatment of epidermoid carcinoma of the anus and anorectum.

Phase-1 trial of high-dose intravenous cisplatin with simultaneous intravenous sodium thiosulfate

SummaryPrevious pharmacological and clinical data have suggested that it is possible to increase significantly the dose of “active” cisplatin delivered systemically by the simultaneous administration of intravenous sodium thiosulfate. In order to define more critically the toxicity and potential efficacy of this therapeutic approach, 36 patients with a variety of solid tumors and limited pretreatment were entered into a phase-1 trial of high-dose intravenous cisplatin plus sodium thiosulfate. The maximally tolerated dose of cisplatin was found to be 200 mg/m2, excessive renal toxicity being observed at a dose of 225 mg/m2 (6/14 courses associated with serum creatinine rise to >2.0 mg-%). Following several courses of high-dose cisplatin, peripheral neuropathy becomes the limiting toxicity (9/15 patients receiving at least three courses of cisplatin at ≧ 150 mg/m2 experienced at least grade-1 neuropathy). Significant ototoxicity developed after only one or two treatment courses, but with continued treatment hearing loss appeared to stabilize in the moderately severe range in most patients. Major responses (PR/CR) were observed in 7/27 evaluable patients. We conclude that cisplatin can be administered at a dose at 200 mg/m2 as a 2-h infusion (with simultaneous sodium thiosulfate) with significant but acceptable toxicities and without evidence of loss of anti-neoplastic activity (secondary to the presence of thiosulfate). However, owing to the development of neurotoxicity most patients will be unable to receive more than three courses of this high-dose treatment regimen.