Tom Anderson

Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy.

Abstract Eighty patients with advanced ovarian adenocarcinoma were treated in a prospective, randomized trial comparing a four-drug combination — hexamethylmelamine, cyclophosphamide, methotrexate and 5-fluorouracil — with the oral alkylating agent, melphalan. Treatment with the four-drug combination was associated with a significantly increased overall response rate (75 vs. 54 per cent) (P<0.05), more complete remissions (33 vs. 16 per cent) and longer median survival (29 vs. 17 months) (P<0.02) but more severe toxicity than occurred with melphaIan. Patients with minimal residual disease had a significantly higher overall response rate than patients with extensive residual disease (84 vs. 53 per cent) (P<0.05). Patients with advanced disease who achieved a complete remission documented by peritoneoscopy or laparotomy (or both) have a median survival that will exceed three years. The four-drug regimen is more effective than melphalan in the management of advanced ovarian adenocarcinoma. (N Engl J Med 299:...

Mutagenicity, cytotoxicity and DNA crosslinking in V79 Chinese hamster cells treated with cis- and trans-Pt(II) diamminedichloride.

The mutagenicity and cytotoxicity of cis- and trans-Pt(II) diamminedichloride (PDD) were examined in V79 Chinese hamster lung cells and compared with effects on DNA measured by alkaline elution. DNA--protein crosslinks and DNA interstrand crosslinks were detected following doses of cis-PDD which reduced cell survival 80--90% and which produced a mutant frequency of 3 X 10(-4) at the HGPRT locus. Equitoxic doses of trans-PDD were much less mutagenic than cis-PDD. At equitoxic doses, trans-PDD produced more DNA-protein crosslinking than did cis-PDD, but interstrand crosslinking for the two isomers was comparable. Hence, the interstrand crosslink could be the cytotoxic lesion produced by these Pt compounds whereas neither of these DNA lesions are necessarily mutagenic. The mutagenesis produced by cis-PDD could be due to crosslinks of a different type than those produced by trans-PDD or it may be due to monofunctional damage.

Hyperkalaemia, a sequel to chemotherapy of Burkitt's lymphoma.

Abstract Hyperkalaemia developing within 48 hours of chemotherapy was found in retrospective analysis in five of twenty-two evaluable cases of Burkitts lymphoma in patients treated in the U.S.A. This syndrome was fatal in two of these five patients, and was the suspected cause of sudden post-chemotherapeutic death in two further cases in which serum-potassium levels were not recorded. Clinical and animal studies suggest that hyperkalaemia is related to sudden lysis of large volumes of tumour. Patients at serious risk were found to be those with large tumour masses and/or impairment of renal function. Close observation, parenteral hydration, and diuretic therapy, control of hyperuricaemia, reduction of the initial dose of chemotherapy, and, if necessary, dialysis are suggested during the initial therapy of these high risk Burkitt lymphoma patients.

Peritoneoscopy: a valuable staging tool in ovarian carcinoma.

Peritoneoscopy was done within 1 month of exploratory laparotomy in 30 consecutive patients, with ovarian carcinoma as part of their pretreatment evaluation. Six of the 7 patients who were thought to have ovarian carcinoma localized to the pelvis (stages I and II) were found to have advanced disease (stage III) at peritoneoscopy and thus required a change in therapy. Metastatic diaphragmatic involvement in ovarian carcinoma is common and was found in 77 percent of all patients studied. The routine shielding if the liver area ordinarily used with total abdominal radiotherapy would select these patients for therapeutic failure. Peritoneoscopy supplied reevaluable finding in 2 of 7 patients having normal physical, roentgenologic, and laboratory examinations, as well as in 93 percent of all patients stuided. Second look peritoneoscopy precluded the need the laparotomy in 5 to 13 patients achieving as apparent clinical remission.

The Role of the Radioimmunoassay of Serum Alpha-Fetoprotein and Human Chorionic Gonadotropin in the Intensive Chemotherapy and Surgery of Metastatic Testicular Tumors

Quantitative measurement of serum alpha-fetoprotein and human chorionic gonadotropin by double antibody radioimmunoassays reflects the efficacy of surgical, radiation and/or chemotherapeutic regimens in patients with bulky disseminated testicular tumors. When these therapies are effective they produce an immediate decrease in serum levels of these markers that reflects the decrease in tumor size and could be as rapid as the catabolic decay rate for alpha-fetoprotein or human chorionic gonadotropin. The alpha subunit of human chorionic gonadotropin has a short half-life (20 minutes) and has been used for the first time to localize a recurrent metastatic testicular tumor. Cellular localization of these markers by immunochemical techniques has helped us to understand the natural history of this cancer and the cell types responsible for production of the markers.

The treatment of Hodgkin's disease

Summary During the past 10–15 years there has been a dramatic improvement in the prognosis of patients with Hodgkins disease. More than 80% of all patients now will live 5+ years, many of them free from disease. The well-recognized immediate complications of staging and therapy, and the potential long-term complications of therapy discussed above, are insignificant compared to the tremendous improvement in patients survival. The fact that they now probably will survive long enough to potentially be at risk of such long-term complications is a testament to the efficacy of modern-day aggressive therapy.

Correlation of Computed Tomography and Serum Tumor Markers in Metastatic Retroperitoneal Testicular Tumor

Preliminary findings of an apparently good correlation between computed tomography and serum tumor markers—human chorionic gonadotropin and alpha fetoprotein—are presented. These findings are from an ongoing prospective randomized study evaluating the efficacy of intensive chemotherapy and cytoreductive surgery in metastatic retroperitoneal testicular germ cell tumors.

Sequential methotrexate, 5-fluorouracil, and calcium leucovorin in colorectal carcinoma

Forty-four patients with locally recurrent or metastatic colorectal adenocarcinoma were treated with methotrexate (MTX) 100 mg/m2 i.v. followed 1 h later by 5-fluorouracil (5-FU) 600 mg/m2 i.v. Calcium leucovorin 10 mg/m2 p.o. q 6 h × four doses was given 24 h after MTX. The regimen was given on days 1 and 8 and repeated every 28 days. Six of 44 patients (14%) obtained either complete or partial response with a mean response duration of 6.8 months. Of 26 previously untreated patients there were one complete response (4%), four partial responses (15%), and 12 (46%) instances of stabilization of disease. Patients obtaining response or stabilization of disease experienced improved survival compared to those with progressive disease. Toxicity consisted of stomatitis and hematopoietic suppression requiring dose attenuation in six patients (14%); there were no treatment-related deaths. Sequenced MTX/5-FU is modestly active with acceptable toxicity in previously untreated patients with colorectal adenocarcinoma but offers no apparent advantage over single-agent 5-FU.

Computed tomography in evolution of testicular cancer during intensive chemotherapy.

The evolution of malignant testicular tumor to mature teratoma has been studied in 4 patients. Computed tomography has been helpful in early diagnosis of this biologic phenomenon in these patients receiving intensive chemotherapy for disseminated non-seminomatous testicular cancer. Although the potential significance of this conversion in terms of survival is not known its early recognition by computed tomography has been useful in selecting and monitoring the therapy of these patients.

Advanced Ovarian Adenocarcinoma A Prospective Clinical Trial of Melphalan (L-PAM) Versus Combination Chemotherapy

Eighty patients with advanced ovarian adenocarcinoma were treated in a prospective, randomized trial comparing a four-drug combination--hexamethylmelamine, cyclophosphamide, methotrexate and 5-fluorouracil--with the oral alkylating agent, melphalan. Treatment with the four-drug combination was associated with a significantly increased overall response rate (75 vs. 54 per cent) (P less than 0.05), more complete remissions (33 vs. 16 per cent) and longer median survival (29 vs. 17 months) (P less than 0.02) but more severe toxicity than occurred with melphalan. Patients with minimal residual disease had a significantly higher overall response rate than patients with extensive residual disease (84 vs. 53 per cent) (P less than 0.05). Patients with advanced disease who achieved a complete remission documented by peritoneoscopy or laparotomy (or both) have a median survival that will exceed three years. The four-drug regimen is more effective than melphalan in the management of advanced ovarian adenocarcinoma.