Roland T. Skeel

Prognostic effect of weight loss prior tochemotherapy in cancer patients

The prognostic effect of weight loss prior to chemotherapy was analyzedusing data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkins lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

125I interstitial implant, precision high‐dose external beam therapy, and 5‐FU for unresectable adenocarcinoma of pancreas and extrahepatic biliary tree

Twelve patients with adenocarcinoma of the pancreas and two patients with carcinoma of the extrahepatic biliary tree received combined therapy with 125I implant, precision high‐dose (PHD) photon external beam therapy, and systemic 5‐fluorouraciI (5‐FU). The 125I implant delivered 120 to 210 Gy (median 140 Gy). PhD external beam therapy was given with high‐energy photons (10, 15 or 45 meVp) and was initiated 4 to 6 weeks postimplant. A dose of 48.6 to 63 Gy was delivered over 5.5 to 7 weeks in 1.8 Gy increments. Six patients received 5‐FU, 500 mg/m2 via weekly intravenous bolus injection. No patient was lost to follow‐up (range, 3.5–57 months). Acute postoperative morbidity included pancreatic fistula in two patients and gastrointestinal tract bleeding, pulmonary embolism, and cholangitis in one patient each. No patient died of radiation complications. Median survival of the patients with pancreas cancer was 15 months. One patient is alive at 41 months with hepatic metastasis. Satisfactory palliation was observed in patients with pancreas cancer treated with 125I interstitial implant followed by PhD external beam photon therapy and 5‐FU. Patient survival did not seem superior to that of patients treated with PhD external beam therapy ± chemotherapy, a less morbid procedure. Two cases of bile duct cancer treated in similar fashion are presented.

Phase II study of cisplatin and 5‐fluorouracil in previously treated metastatic breast cancer: an Eastern Cooperative Oncology Group study (PA 185)

Purpose: The present study was conducted to investigate the efficacy and toxicity of a cisplatin and 5‐fluorouracil (5‐FU) combination in previously treated advanced breast cancer.Methods: Thirty‐six women with recurrent metastatic breast cancer were entered on a phase II study of 5‐FU 1000 mg/m2/day given intravenously as a continuous infusion on days 1–3 and cisplatin 30 mg/m2/day given intravenously over 1 h on days 2–4, repeated every 21 days. All subjects had received one previous chemotherapy regimen for metastatic disease and either progressed during treatment or relapsed after responding to previous chemotherapy. Fourteen patients had also received previous adjuvant chemotherapy, 17 patients had previous radiation therapy, and 29 patients had previous hormonal therapy.Results: Among 32 response‐evaluable patients, there were 10 partial remissions (31%) and 1 complete remission (3%), with an overall objective response rate of 34%. Median duration of response was 4 months. Median survival was 10.5 months for responders and 9.5 months for the entire group. Toxicity was mild to moderate in most patients. Overall twelve patients experienced grade 3 toxicity (10 hematologic, 1 mucositis, and 2 nausea). There were no grade 4 or 5 toxicities.Conclusion: Infusional cisplatin and 5‐FU is a well tolerated and active regimen in women with previously treated advanced breast cancer.

Concomitant radiation therapy and constant infusion FUdR for unresectable hepatic metastases.

Ten patients with unresectable liver metastases from intraabdominal primary malignancies were treated with combined hepatic irradiation and hepatic artery infusion with FUdR using an Infusaid pump. The median survival for the entire group was 10 months. Four (40%) demonstrated an objective response to treatment: Three patients had a decrease in tumor mass on computed tomography (CT) scan, and one patient had a reduction in liver size as measured by palpation. The survival of two of the three patients whose tumor size was observed to be reduced on CT scan was significantly longer than that of the rest of the group (23, 37, and 12 months). Treatment was generally well tolerated with only mild side effects. Morbidity from chemotherapy did not appear to be enhanced by combination with hepatic irradiation. This form of treatment, although it has not demonstrated improved survival compared with other treatments in this setting, may be considered for adjuvant therapy in patients with hepatic metastases.

Phase II trials of Baker's antifol, bleomycin, CCNU, streptozotocin, tilorone, and 5-fluorodeoxyuridine plus arabinosyl cytosine in metastatic breast cancer.

A total of 202 patients with advanced breast cancer were entered into two prospectively randomized Phase II trials conducted by the Eastern Cooperative Oncology Group, in an effort to identify promising agents and combinations for previously treated cases. Patients in Study 1 received bleomycin, CCNU, or streptozotocin and those in Study 2 received tilorone, Bakers antifol, or a combination of 5‐fluoro‐deoxyuridine plus arabinosyl cytosine. Partial responses were seen only with bleomycin, Bakers antifol, and 5‐fluorodeoxyuridine plus arabinosyl cytosine. The median times to treatment failure ranged from 3.6 weeks to 5.7 weeks, and the median survival times, from 8 weeks to 25 weeks for tilorone and bleomycin, respectively. Toxic reactions was primarily hematologic and gastrointestinal, but skin, neurologic, respiratory, and renal abnormalities were noted in some treatment arms. The treatment schedules outlined and the toxic effects noted provide background information that might prove useful in designing complex new chemotherapeutic programs, since there is pharmacological rationale for incorporating some of the agents tested into present standard combination chemotherapy regimens.

Cyclophosphamide, cytosine arabinoside and methotrexate versus cytosine arabinoside and thioguanine for acute non-lymphocytic leukemia in adults.

One‐hundred and fifty‐one adults with acute non‐lymphocytic leukemia (ANLL) were entered into an Eastern Cooperative Oncology Group protocol (EST‐1473) comparing twice daily cytosine arabinoside and thioguanine (AT) with weekly cyclophosphamide, cytosine arabinoside, and methotrexate (CAM) for remission induction. Of 111 evaluable patients, 16 treated with CAM and 16 treated with AT entered complete remission (CR) on their initial therapy and 5 additional patients entered CR on crossover for a total of 37 or 33% of the evaluable patients. Of the 71 patients who survived three weeks or longer, the overall CR rate was 52%. Cytochemical studies were performed on 85% of the evaluable cases. Minor disagreements between morphologic subtypes of ANLL occurred in 50% of cases. There was no difference in response rates between the major subtypes of ANLL regardless of whether the investigators diagnosis or the cytochemical reference laboratory diagnosis was used. The median survival of all evaluable patients was 4.9 weeks; those patients who responded with a CR had a median survival of 60 weeks, while those who did not have a median survival of <3 weeks. Age <60, ambulatory performance status, or fewer than 50% marrow blasts were also associated with a better response rate and longer survival. CAM had more severe mucositis and vomiting associated with it than did AT, but toxicities were otherwise comparable. Weekly CAM and AT appear to be equally effective regimens in the treatment of ANLL.

Conventional dose melphalan is inactive in metastatic melanoma: results of an Eastern Cooperative Oncology Group Study (E1687).

Despite reports that i.v. melphalan is active in the settings of conditioning regimens utilizing high-dose chemotherapy for autologous bone marrow transplantation and in isolated limb perfusion for the treatment of malignant melanoma, its activity at conventional doses has never been defined in this disease. We conducted a phase II study of conventional-dose i.v. melphalan (30 mg/m2) in 17 patients with metastatic melanoma. All patients were previously untreated with chemotherapy with performance status 0, 1 or 2. Forty-seven cycles were given with a median of two cycles. One patient was not evaluable due to early death. There were no responses in the 16 patients, resulting in a 0% response rate (95% confidence interval = 0-17%). We conclude that conventional-dose melphalan by i.v. administration has no appreciable activity in patients with metastatic malignant melanoma.

A Phase II Study of Carboplatin and CHIP in Patients with Metastatic Colon Carcinoma

Fifty-six patients were treated in each arm of a study comparing CHIP and carboplatin for the therapy of previously untreated metastatic colorectal carcinoma. There were one partial response (2%) with CHIP and two partial responses (4%) with carboplatin. Side effects were significantly more severe with CHIP than with carboplatin. The most common side effect for both drugs was vomiting followed by hematologic side effects. Sixteen percent of the patients receiving CHIP and 9% of those receiving carboplatin had life-threatening side effects. Neither drug offers significant activity in metastatic colorectal carcinoma.

Primary CNS lymphoplasmacytic lymphoma: a case report and review of literature.

Lymphoplasmacytic lymphoma is a chronic lymphoproliferative disorder characterized by a proliferation of plasma cells, small lymphocytes, plasmacytoid lymphocytes and the production of monoclonal IgM. Primary central nervous system lymphomas (PCNSL) are rare non-Hodgkin lymphomas (NHL) that can be found in the brain, leptomeninges, eyes or spinal cord, and are mostly intracerebral. PCNSLs constitute 3-4% of primary brain tumors, and in most cases are diffuse large B-cell lymphomas (DLBCL).(1) Low grade lymphomas as primary central nervous system (CNS) lymphoma are very rare. We present here a case report of a woman who presented with headache and was found to have primary intracranial lymphoplasmacytic lymphoma (LPL).

Priapism in a child with chronic granulocytic leukemia

Summary A child with chronic granulocytic leukemia and priapism is presented to emphasize the rarity of this associated symptom-disease complex. Radiation therapy to the penile area resulted in a prompt abatement of this complication before hematologic control of the underlying disease was achieved with busulfan. There was no recurrence of priapism even at the time of relapse and during the accelerated terminal phase of the illness. The possible etiology of this rare condition is discussed.