Chylous ascites following retroperitoneal lymph node dissection successfully treated with peritoneovenous shunt.

A massive lymphatic leak developed following radical retroperitoneal lymph node dissection for recurrent extragonadal seminoma. Chylous ascites persisted for over 3 months, with an average daily external drainage of 1.5 liters, and was successfully treated with a peritoneovenous shunt.

Eastern Cooperative Oncology Group: a comparison of adjuvant doxorubicin and observation for patients with localized soft tissue sarcoma.

Forty-seven patients with stage I, II, or III soft tissue sarcoma were entered into a prospective randomized Eastern Cooperative Oncology Group (ECOG) adjuvant protocol. Eligibility included conservative or radical primary treatment for local cure. Patients were then randomized to control or Adriamycin (Adria Laboratories, Columbus, OH). Adriamycin was administered at 70 mg/m2 (slow push, every 3 weeks for seven courses for a maximum of 550 mg/m2). To date, 32 patients, 17 males and 15 females, with an age range of 17 to 75 years (median, 44 years) have been followed sufficiently long to be included in this analysis. Nine patients have died. The median follow-up of the remaining 23 patients is 30 months (range, 2 to 50 months). Survival was not significantly different between Adriamycin or control. However, the disease-free interval was slightly different in favor of observation. This preliminary report does not support the hypothesis that Adriamycin is an effective adjuvant therapy for soft tissue sarcoma. Due to the small numbers, these results must be interpreted in relation to our ability to detect a difference, if in fact one existed. These preliminary data suggest that adjuvant Adriamycin not be used outside the confines of a clinical trial such as the current intergroup adjuvant sarcoma study.

Phase II evaluation of dibromodulcitol and actinomycin D, hydroxyurea, and cyclophosphamide in previously untreated patients with malignant melanoma.

In this Eastern Cooperative Oncology Group (ECOG) phase II study, dibromodulcitol (DBD) and a combination of actinomycin D, hydroxyurea, and cyclophosphamide (AHC) were compared with methyl-CCNU, the current ECOG standard, in patients who had received no prior chemotherapy for disseminated malignant melanoma. The response rates were 6% (3/50) for AHC, 9% (3/34) for DBD, and 14% (7/49) for methyl-CCNU. Median survival times were 4, 5, and 6 months, respectively. Neither regimen appears to offer any advantage over methyl-CCNU as front-line therapy for patients with disseminated melanoma.

A logistic model based on enzyme activities for the prediction of response of breast cancer patients to chemotherapy.

A logistic regression model, utilizing the activities of certain selected glycolytic enzymes and ER status measured on primary or recurrent lesions, has been applied to predict for response to combination chemotherapy regimens administered to women with advanced breast cancer. The clinical outcome of response or no response was evaluated retrospectively using criteria employed by cooperative group protocols. In 93 cases, 58/61 patients classified as nonresponders and 22/32 patients demonstrating objective responses would have been correctly designated, based on the 50% estimated probability as the level for separation of responders from nonresponders. The overall predictive accuracy of this model was 86%, with apparently greater accuracy for prediction of lack of response. Addition of estrogen receptor status to the model imparted no gain in accuracy of prediction. Application of this model to a prospective study is warranted.

Peritoneovenous shunt for palliation of malignant ascites.

Forty patients with malignant ascites refractory to conventional medical management had peritoneovenous shunt for palliation. The shunt provided effective palliation in 28 with decrease in weight, abdominal girth, number of paracenteses required and increase in urine output. These patients also had improvement in strength, appetite and ambulation. Complications such as hemodilution, volume overload, and sepsis do not contraindicate surgery. In 12 patients with high ascitic fluid protein content (4.5 g/liter) and a large number of malignant cells, loculated ascites and prior severe renal and cardiac disease, the shunt did not provide palliation. Peritoneovenous shunt appears to provide effective palliation in carefully selected patients with refractory malignant ascites.

Low tissue enzyme activity seen in breast cancers of patients who fail adjuvant chemotherapy.

Primary breast cancers from 54 patients undergoing postsurgical adjuvant chemotherapy were analyzed for several enzymes and estrogen receptors to determine if biochemical parameters might offer a prognostic index for determining outcome of therapy. Recurrence of disease during therapy or within 12 months after cessation of therapy was the criterion for classifying the patient as a treatment failure. Recurrence rates were similar in ER-positive vs. ER-negative patients, indicating that estrogen receptor status offered no predictive value in this series. However, patients who failed therapy had tumors that displayed significantly lower activities of lactate dehydrogenase, glucosephosphate isomerase, and glucose 6-phosphate dehydrogenase vs. patients who showed no evidence of recurrence for this observation period. When either premenopausal or ER-negative patients were compared, a similar observation was made; low enzyme activities occurred in patients failing to benefit from adjuvant chemotherapy. Based on this series of patients, it is suggested that a selected enzyme activity profile may offer a predictive index for recurrence in the adjuvant chemotherapy setting.

Comparison of doxorubicin with cycloleucine in the treatment of sarcomas.

In this patient series, doxorubicin and cycloleucine at a dose of 300 mg/kg both show response rates in the treatment of advanced soft tissue sarcomas of about 15%. Lower doses of cycloleucine (200 mg/kg) yielded less toxicity but were less effective against the sarcomas (6% response rate, three of 51 patients). There were no complete responses with cycloleucine and there were three with doxorubicin. Survival times for patients receiving doxorubicin were significantly longer than those of patients receiving cycloleucine at doses of 300 mg/kg (P less than 0.001) or 200 mg/kg (P = 0.02). The estimated survival times were 29 weeks for doxorubicin and 21 (300 mg/kg) and 18 (200 mg/kg) weeks for cycloleucine. Toxic effects due to cycloleucine were excessive, with severe thrombocytopenia and central nervous system depression being the most prominent.

The lack of relationship between estrogen receptor status and response to chemotherapy.

The possible relationship between estrogen receptors and response of breast cancer patients to chemotherapy was examined in two situations: patients with advanced disease and patients receiving post-surgical adjuvant treatment. In 73 patients with disseminated disease, no relationship between ER status and response to cytotoxic chemotherapy was observed. At this time, 44 of these cases have undergone extramural review; in these 44 cases, we observed no significant relationship between ER status and response to chemotherapy. In a series of 52 patients receiving adjuvant therapy, 27 patients were classified as failures due to recurrence. ER status did not offer prognostic value for failure of patients treated with postsurgical adjuvant therapy. We conclude that the prognostic value of ER data in nonhormonal therapy settings remains to be proven

Treatment of carcinoma of the rectum and squamous carcinoma of the anus by combination chemotherapy, radiotherapy and operation.

After reviewing the recent literature, a protocol has been formulated at this hospital for patients with carcinomas of the anus and rectum larger than 5 centimeters in diameter. The protocol used in this study was a combination of chemotherapy and radiation therapy, followed four to six weeks later by abdominoperineal resection. This approach has been demonstrated clearly to be of value. All lesions decreased in size. In more than half the number of patients, the primary lesion was reduced by more than 50 per cent; 78 per cent of the patients had no nodes at operation. In ten patients, there was no tumor and, in 26, only minimal tumor. We have the impression that, if operation were delayed another two weeks, perhaps even some of these patients would have had no tumor. It is too early to be able to consider five and ten year results. However, at the same time, present results demonstrate most effectively the value of combined interdisciplinary therapy by means of the available modalities in the management of carcinoma of the rectum and anus.

The relative importance of estrogen receptor analysis as a prognostic factor for recurrence or response to chemotherapy in women with breast cancer.

The value of estrogen receptor (ER) analysis in primary breast cancer samples as a potential prognostic factor was examined in three clinical situations: time to recurrence in patients with no therapy after mastectomy, failure of patients receiving adjuvant therapy, and response of advanced disease patients to cytotoxic chemotherapy. Other prognostic factors analyzed were menopausal and nodal status. In none of these clinical settings were we able to demonstrate the usefulness of ER status as a prognosticator of the disease course or its response to therapy.

A statistical model for predicting response of breast cancer patients to cytotoxic chemotherapy.

A binary logistic model is used for predicting response to cytotoxic chemotherapy for a breast cancer patient on the basis of her tumor enzyme activity profile. The enzymes used in the model are lactate dehydrogenase, nicotinamide adenine dinucleotide phosphate-isocitrate dehydrogenase, and phosphoglucomutase, all of which were measured on primary tumor specimens from each patient. The statistical model provides an estimate of the probability that an individual will respond to treatment. Chemotherapeutic treatment consisting of combination cytotoxic drugs and subsequent evaluation of patient response followed cooperative group protocol guidelines, including outside review to confirm the patient evaluation. The model based on this study, which represents 5 years of patient follow-up, correctly predicts clinical outcome in 32 of the 37 cases available.

Phase II study of vinblastine, methyl-CCNU, and medroxyprogesterone in advanced renal cell cancer.

One hundred and sixty-five patients with advanced renal cell cancer were evaluable for combination or single-agent therapy with methyl-CCNU, vinblastine, and medroxyprogesterone. A low order or response was observed, and these agents were not proven effective as treatment for metastatic renal cell cancer. Performance status and a relatively long symptom-free interval from primary tumor to metastatic disease were found to be the most prognostically significant factors for survival.

PIP: Patients with metastatic renal cell cancer have an overall 5-year survival rate of only 28% to 40% in spite of aggressive surgical treatment. A prospective randomized study conducted by the Eastern Cooperative Oncology Group used methyl--CCNU (meCCNU), vinblastine, and meCCNU-medroxyprogesterone acetate (MPA) to treat 165 patients with advanced renal cancer. The antitumor activity of the single-agent and/or combination therapy is analyzed. Patients were classified (as to grade of anaplasia of tumor; age; performance status; primary site of metastatic disease; and previous treatment with a progestational agent) and randomly assigned to various treatment protocols as described. Crossover randomization to one of alternate single-agent or combination regimens was carried out after failure with initial therapy. 2 meCCNU regimens were associated with severe hematologic toxicity, vinblastine regimens with neurotoxicity. All regimens except the vinblastine-MPA resulted in substantial vomiting. Response rate is low (11%) with each regimen. There were no statistically significant differences in treatment variables or factors among the various regimens. Patients capable of normal activity had a significantly higher response rate and longer survival period than nonambulatory or poor performance status patients. A relatively long symptom-free interval from primary tumor to metastatic disease was also associated with better survival rate. More than 50% of patients exhibited disease progression with 3 months of initiating the regimens.

Further studies of biochemical predictive tests in breast cancer.

This report extends our observations on the relationship between the therapy of breast cancer, estrogen binding and tissue enzymes. We have compared the dextran-coated charcoal method and the sucrose gradient analysis in determining estrogen receptors, and find a sub-group of receptor positive tumors--identifiable only by the latter technique--which we suggest may lead to an incorrect prediction of response to hormonal therapy. Data are also presented to suggest that enzyme analyses show promise in predicting responsiveness to present modes of combination chemotherapy of breast cancer.

Relationship of glycolytic enzyme activities and response of breast cancer patients to chemotherapy: A preliminary report.

Activities of glucosephosphate isomerase, lactate dehydrogenase, and NADP-isocitrate dehydrogenase were significantly elevated in breast cancer specimens from patients who responded favorably to combination cytotoxic chemotherapy regimens compared with those in carcinomas from patients failing to respond to the same chemotherapy. Presence of estrogen receptors and clinical response to hormonal therapy were also evaluated in neoplasms from these patients. The data suggest that measurement of the enzyme profile, along with estrogen receptor levels, may be useful in selecting a mode of therapy for patients with advanced disease.