Octreotide LAR resolves severe chemotherapy-induced diarrhoea (CID) and allows continuation of full-dose therapy.

Severe diarrhoea after chemotherapy is a dose-limiting toxicity of first-line chemotherapeutic agents approved for the treatment of colorectal cancer including 5-fluorouracil + leucovorin (5-FU/LV) and irinotecan (CPT-11). This report explores the potential of the long-acting version of the somatostatin analogue octreotide, for secondary prophylaxis in patients suffering from chemotherapy-induced diarrhoea (CID). A case series of three patients in a general community setting with colorectal cancer and severe refractory diarrhoea after fluoropyrimidine or irinotecan therapy resulting in suspension of chemotherapy, hospitalization, and/or refusal of further treatment. After the failure of initial aggressive antidiarrhoeal therapy with loperamide and/or diphenoxylate-atropine, patients were treated with octreotide LAR (30 mg q28d). The ability of octreotide LAR to resolve diarrhoea, prevent further episodes of grade 3 or 4 gastrointestinal toxicity and prevent costly hospitalizations. Octreotide LAR 30 mg q28d speed resolution of diarrhoea and was able prevent further episodes during subsequent cycles of chemotherapy. One patient who initially refused chemotherapy because of CID was able to complete his treatment. All patients reported improvement in quality of life following resolution of diarrhoea with octreotide LAR and no further hospitalizations because of CID were necessary.

Phase II trial of amonafide in patients with advanced metastatic or recurrent endometrial adenocarcinoma. A Southwest Oncology Group study.

Amonafide, a benzisoquinoline-1,3-dione was administered to 38 patients with recurrent or metastatic, bidimensionally measurable endometrial cancer. There were 34 patients with no prior cytotoxic chemotherapy, performance status of 0-2, and normal bone marrow, renal, and hepatic function were eligible for response and toxicity evaluation. Amonafide, 300 mg/m2, was administered intravenously over 1 hour daily for 5 consecutive days. Courses were repeated every 21 days. The major grade 3 or 4 toxicities were hematologic with granulocytopenia in 18 patients (53%), thrombocytopenia in 6 patients (18%), and anemia in 8 patients (24%). Infectious complications occurred in 3 patients (9%). Other side effects included cardiac dysrhythmias, hypotension, pain and phlebitis at the site of injection, nausea, vomiting, and flu-like symptoms. The overall objective response rate was 6% (95% confidence interval of 1-20%); 2 patients had a complete response (6%), 9 patients had stable disease (26%) and 21 patients had progressive disease (62%). Two patients had insufficient follow-up for response determination and are assumed to be nonresponders. The median survival of the eligible patients was 8 months. With the toxicity observed and the low response rate, amonafide at this dose and schedule has no efficacy in the treatment of endometrial cancer.

A phase II trial of ftorafur: adriamycin and mitomycin-C (FAM II) in advanced gastric adenocarcinoma.

Fifteen patients with advanced gastric cancer were treated with the combination of Ftorafur, Adriamycin and mitomycin-C (FAM II). Three patients showed partial responses, in five the disease remained stable for at least 3 months and seven showed progression while on treatment. All responding patients showed survival in excess of 12 months. Hematologic toxicity was of only moderate severity. Median white count nadir was 3500 cells/mm3 and median platelet nadir was 187,000 cells/mm3. Four patients had white count nadirs from 2000--2500 cells/mm3 and three had nadirs from 500--1500 cells/mm3; also there were four with platelet nadirs less than 100,000/mm3. However, no drug-related infections occurred and no platelet transfusions were required. The major non-hematologic toxicities of the regimen were nausea, vomiting, dizziness, vertigo, and rhinorrhea. These toxicities were limiting and resulted in termination of the trial because of poor patient acceptance and the failure of the combination to exhibit a therapeutic advantage over the similar combination (FAM) that employed weekly 5-fluorouracil in place of Ftorafur.

Peritoneoscopy: a technique to evaluate therapeutic efficacy in non-Hodgkin's lymphoma patients.

Peritoneoscopy was performed in 22 patients with non-Hodgkin's lymphoma as a re-staging technique to rule out relapse or persistence of active disease after intensive chemotherapy and/or radiotherapy. Fifteen patients with previous hepatic involvement achieved a complete clinical remission; however, five patients (33%) had persistent disease proved by biopsy at peritoneoscopy. In seven patients suspected to have a clinical relapse, peritoneoscopy biopsies documented relapse in three patients (43%), including two patients with negative percutaneous liver biopsies. Because of its low morbidity rate (4%), peritoneoscopy can be utilized to re-stage hepatic involvement by non-Hodgkin's lymphoma patients more accurately than percutaneous liver biopsies and with less morbidity than laparotomy.

Use of peritoneoscopy for initial staging and posttherapy evaluation of patients with ovarian carcinoma.

Forty patients with ovarian adenocarcinoma had peritoneoscopy within 1 month of their exploratory laparotomy as part of their pretreatment evaluation. Of 12 patients (58%) believed to have disease localized to the pelvis (stage 1 or II) at laparotomy staging 7 were found to have more advanced disease (stage III) at peritoneoscopy and thus required a change in therapy. Involvement of the diaphragm with metastatic ovarian carcinoma was found in 63% of all patients. This finding again necessitated a change in therapy, since the right hemidiaphragm is shielded along with the liver when abdominal radiotherapy is used. Peritoneoscopy supplied the only followable findings with which to gauge response to therapy in 40% of the patients and also supplied followable findings in 78% of all patients studied. Second-look peritoneoscopy was performed in all patients achieving an apparent clinical remission with chemotherapy. Active disease was found in 43% of these patients, which thus precluded the need for laparotomy.

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.

Adriamycin-induced cardiac damage in the mouse: a small-animal model of cardiotoxicity.

After one dose of adriamycin, a subacute cardiomyopathy was observed in the mouse by both light and electron microscopy. The microscopic alterations were characterized by single-cell necrosis and mitochondrial degeneration. These lesions were similar to those seen in man and shortly preceded fatal toxicity.

Recovery of normal hematopoietic tissue and tumor following chemotherapeutic injury from cyclophosphamide (CTX): comparative analysis of biochemical and clinical techniques.

Simultaneous alterations in the incorporation of 3H-thymidine (3H-TdR) into DNA are induced by CTX in normal host target tissues and L1210 ascites tumor. The timing of suppression and recovery of these nucleoside incorporation alterations was similar at the three CTX doses studied, but some evidence for a dose-response effect was seen as the magnitude of suppression of DNA synthesis increased with increasing dosage. A differential pattern of suppression and recovery of 3H-TdR incorporation in malignant and normal host tissues was observed. The pattern of suppression and recovery of the peripheral white blood count and bone marrow (BM) cellularity, two frequently studied clinical parameters of hematopoietic recovery, were out of phase with the recovery of BM-DNA synthesis and failed to accurately reflect the sensitivity of the BM to subsequent chemotherapeutic injury. In contrast, drug schedules based on the differential recovery patterns of the host tissues and tumor, reflected by their 3H-TdR incorporation into DNA, both reduced toxicity to normal mice and increased the survival of tumor-bearing animals.

Percutaneous liver biopsy, peritoneoscopy and laparotomy: an assessment of relative merits in the lymphomata.

The relative merits of percutaneous liver biopsy, peritoneoscopy directed liver biopsy and wedge liver biopsy during laparotomy were examined in a series of 100 consecutive untreated patients with non-Hodgkin's lymphoma. Sixteen of 77 patients had positive findings on percutaneous liver biopsy specimens, with the best yield in patients with nodular (21%) and diffuse (33%) poorly differentiated lymphocytic lymphoma. Forty-nine of the 61 patients having negative percutaneous biopsies were subjected to peritoneoscopy and 9 additional positive biopsies were obtained. Thirty-two of the 40 patients having negative percutaneous and peritoneoscopy findings underwent laparotomy and wedge biopsy of the liver, and 8 specimens (25%) were positive for liver involvement; all but one of these were in patients with nodular or diffuse poorly differentiated lymphocytic lymphoma. This study indicates that over two-thirds of untreated patients with non-Hodgkin's lymphoma can be shown to have Stage IV disease without undergoing laparotomy, and that in the remaining patients, laparotomy proved of consistent value only in patients with poorly differentiated lymphocytic lymphoma.

The effect of chemotherapy on the kinetics and proliferative capacity of normal and tumorous tissues in vivo.

The proliferative state of a given tissue is a major determinant of its sensitivity to both phase-specific and cycle-specific chemotherapeutic agents. To study the extent of injury induced by antitumor agents to normal and tumorous tissues, a technique for following DNA synthesis as reflected in the incorporation of tritiated thymidine (3H-TdR) into DNA was compared to the conventional radioautographic technique of the labeling index (LI) and to the functional kinetic technique of granulocyte colony formation in vitro. Alterations in DNA synthesis induced by a single dose of cyclophosphamide in normal and tumorous tissues in vivo paralleled in many respects the changes seen when the more time-consuming techniques of the LI or granulocyte colony formation were employed. However, the recovery of granulocyte colony formation after cyclophosphamide therapy lagged behind the recovery of DNA synthesis in the bone marrow, obscuring a kinetic event of potential therapeutic significance. The determination of DNA synthesis simultaneously in normal and tumorous tissues in vivo was easy to perform and supplied therapeutically pertinent results comparatively quickly.