An epidemiological review of red cell transfusions in cancer chemotherapy.

OBJECTIVE: The objective of this chart review was to determine the frequency of transfusion and prevalence of anemia (hemoglobin result < 100 g/L) in patients receiving chemotherapy. DESIGN: This study was a retrospective review of medical charts. SETTING: Patients receiving chemotherapy were included from 12 tertiary care comprehensive cancer centres across Canada. MAIN OUTCOME MEASURE: The primary study outcome measure was red blood cell transfusion rate, controlling for patient variables. RESULTS: The 616 patients included had started chemotherapy in January-June 1992. For each subject, data collection finished 4 weeks after the end of the first regimen or after a maximum follow-up period of 26 weeks. Seventy-two patients (12%; 95% confidence interval 9.5% to 14.5%) were transfused for anemia (reasons other than blood loss), and 28% (95% confidence interval 24.5% to 31.5%) of the subjects were anemic during treatment. The univariate analyses of transfusion for anemia yielded significant associations with prognostic factors. In the multivariate analyses, platinum (odds ratio [OR] = 6.69) and anthracycline (OR = 3.56) chemotherapy, baseline hemoglobin (OR = 0.96) and disease stage (OR = 1.72) were statistically significant contributors. CONCLUSION: In this patient cohort, red blood cell transfusion was infrequent (12%). However, patient groups at high risk of transfusion could be identified, with platinum-based chemotherapy being the most significant contributing factor. The information obtained from this multicentre study may prove helpful in developing supportive care guidelines for the management of chemotherapy-related anemia requiring transfusion.

Phase I-II study of 5-fluorouracil, leucovorin, doxorubicin, methotrexate, and long-term oral etoposide (FLAME) in unresectable or metastatic gastric cancer.

The objective of this phase I-II study was to determine the efficacy and toxicity of combination chemotherapy with 5-fluorouracil, leucovorin, doxorubicin, methotrexate, and oral etoposide (FLAME) in patients with measurable unresectable or metastatic gastric cancer. Starting doses on the phase I study were as follows: methotrexate 50 mg/m2 intravenous bolus day 1; leucovorin 20 mg/m2 intravenous bolus days 2 through 4, starting 24 hours after the methotrexate dose; 5-fluorouracil 325 mg/m2 intravenous bolus 15 minutes after leucovorin days 2 through 4; doxorubicin 25 mg/m2 intravenous bolus day 8; and oral etoposide 50 mg/day for 14 days, starting on day 8. A new cycle started on day 28. A total of 42 patients were treated--10 patients in the phase I study and 32 patients in the phase II study. Dose-limiting toxicity was encountered in the phase I study on the second escalation step, when doxorubicin was escalated to 30 mg/m2 and 5-fluorouracil was escalated to 350 mg/m2. In the phase II study 28 patients (109 courses) were evaluable for toxicity. Neutropenia grade 3 or more was dose limiting and was documented in 12 patients (43%) during 22 treatment courses (20%). Neutropenia was associated with febrile neutropenia requiring hospitalization in four patients during five courses of therapy. Grade 3 stomatitis and grade 3 diarrhea was infrequent, documented in two patients (two courses) and three patients (four courses), respectively. All other toxicity was grade 1 and grade 2. The combined objective response rate in 38 evaluable patients entered in both studies was 23.3% (six partial responses and one complete response). Stable disease was documented in 15 patients (39.5%). The median survival for the 42 patients entered in both trials was 6.9 months (95% confidence interval, 5.9-8.5 months). The objective response rate and median survival for the combined group is comparable with that reported for the etoposide, leucovorin, and 5-fluorouracil (ELF), and 5-fluorouracil and methotrexate (FMTX) regimens in a recently reported, multicenter, phase III study.

5-FU or UFT combined with leucovorin for previously untreated metastatic colorectal Ca.

This phase III study compares leucovorin plus fluorouracil (5-FU) 425 mg/m2, days 1 through 5, 28-day cycle, with oral leucovorin plus oral UFT (tegafur and uracil) 300 mg/m2, days 1 through 28, 35-day cycle, in terms of efficacy, safety, quality of life, and pharmacoeconomics. Eligible patients have not been treated previously and have measurable or evaluable metastatic colorectal cancer, an Eastern Cooperative Oncology Group performance status of 2 or less, and adequate bone marrow, liver, and renal functions. Patients are evaluated for response clinically and by computed tomography. Responses are determined by World Health Organization criteria. The study is nearing completion, with no toxicity issues requiring protocol modification. The results of this study could lead to a change to oral therapy as the standard of care for metastatic colorectal cancer, providing the efficacy and toxicity of UFT/leucovorin are at least equivalent due to the ease of administration and patient preference for oral regimens.

The effect of socioeconomic status on the long-term outcome of cancer.

This study reports the 8- to 10-year follow-up of male and female patients between the ages of 25 and 70, admitted to two Ontario Regional Cancer Centres with newly diagnosed cancers of a number of common sites. Information was gathered by interview on education, occupation, and chronic illnesses other than cancer. Stage of disease at diagnosis, exact pathologic diagnosis, date of diagnosis, treatment before and after clinic admission, and status of each patient on the last date for which information was available were obtained from clinic charts. Cox's proportional hazards model was used to examine the relationship between socioeconomic status (SES) and duration of survival, with adjustment for other significant prognostic factors. For breast and prostate, there is weak evidence that high SES is associated with improved survival; for other sites, there is no evidence that SES affected survival.

Escalated as compared with standard doses of doxorubicin in BACOP therapy for patients with non-Hodgkin's lymphoma.

BACKGROUND AND METHODS: In 1981 the Clinical Trials Group of the National Cancer Institute of Canada completed a pilot study in patients with advanced-stage non-Hodgkin's lymphoma with aggressive tumor histology. That study demonstrated the potential efficacy of escalating the dose of doxorubicin used in a regimen of bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisone (BACOP). In the present study, we compared standard BACOP (s-BACOP) with BACOP that included escalated doses of doxorubicin (esc-BACOP) in 238 patients 16 to 70 years old with previously untreated, advanced-stage intermediate- or high-grade non-Hodgkin's lymphoma. During the first 28-day cycle all patients received doxorubicin in a dose of 25 mg per square meter of body-surface area on days 1 and 8. Patients randomly assigned to receive s-BACOP subsequently received five identical cycles, whereas those assigned to receive esc-BACOP received 40 mg of doxorubicin per square meter on days 1 and 8 of five subsequent cycles if granulocytopenia (< 1000 cells per cubic millimeter) had not developed during the first cycle. RESULTS: The 119 patients assigned to the esc-BACOP regimen received doxorubicin at a significantly higher mean weekly dose intensity (13.5 vs. 10.4 mg per square meter per week, P < 0.001) and mean total dose (296 vs. 231 mg per square meter, P < 0.001). Because of granulocytopenia during the first cycle of therapy, only 56 of these patients (47 percent) received the escalated doses of doxorubicin. During a median follow-up of 65 months, there were no differences between the s-BACOP and esc-BACOP groups in response rate, overall survival, or survival without disease progression. When the patients who actually received the escalated doses of doxorubicin were compared with the patients in the s-BACOP group in whom neutropenia did not develop during the first treatment cycle, no difference between their outcomes was observed. Toxicity was greater in the esc-BACOP group. CONCLUSIONS: In patients with advanced-stage intermediate- or high-grade non-Hodgkin's lymphoma, escalating the dose of doxorubicin in the BACOP regimen increases toxicity but does not improve the rate of response or survival.

The frequency of red cell transfusion for anemia in patients receiving chemotherapy. A retrospective cohort study.

The objective of this retrospective cohort study was to determine the frequency of red cell transfusion for anemia and risk factors. It was conducted at a regional cancer center and host hospital. All patients receiving chemotherapy in 1989 were studied. Complete data were available on 381; 26 were excluded. Age, diagnosis, baseline and nadir hemoglobin, transfusion history, chemotherapy regimen, and prior treatment were abstracted from the cancer center chart and hospital medical records. Transfusion for anemia was required in 18% of all patients with solid tumors; those with lung cancer had the highest rate (34%). Patients with anemia who entered chemotherapy were more likely to be transfused. Therefore, patients with leukemia, lung cancer, and/or prior anemia have higher transfusion rates and may benefit from such therapies as recombinant human erythropoietin.

Jaw and other orofacial pain in patients receiving vincristine for the treatment of cancer.

This prospective cohort study investigated orofacial pain occurring as a manifestation of vincristine neurotoxicity. Forty cancer patients (28 to 63 years of age) receiving vincristine were given baseline interviews and orofacial examinations, which were repeated weekly for 7 weeks of treatment. Twenty-two patients (55%) had neurotoxicity manifesting as orofacial pain. Onset was usually 3 days after vincristine administration; mean duration was 2 days. Twenty patients (50%) were affected in the first week: nine (22%) with severe and five (12%) with moderate pain. Symptoms were mild and infrequent in subsequent weeks. Eighteen control patients receiving chemotherapy without vincristine had no comparable orofacial symptoms. Multiple sites in the distribution of the trigeminal and glossopharyngeal nerves were affected: primarily the temporomandibular joint, mandible, throat, ears, and mandibular teeth. The frequency of orofacial pain increased with younger age. Pain was significantly associated with smaller body surface area (p less than 0.05), indicating a dose-related toxicity, and with sociodemographic variables including smoking (p less than 0.05).

Orofacial complications of chemotherapy for breast cancer.

The National Institutes of Health recently recommended research initiatives to investigate oral complications of cancer chemotherapy. This prospective cohort study investigated orofacial complications of combination chemotherapy (cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone) in women with breast cancer. Thirty-four patients were given baseline interviews and examinations. Each patient was given weekly orofacial examinations and biweekly interviews for the first seven cycles of cytotoxic treatment. The orofacial complications included neurotoxicity caused by vincristine, mucositis, and candidiasis. Neurotoxicity affected 22 of 34 (65%) patients, was significantly associated with age less than 50 years (p less than 0.05), and manifested as pain in 19 of 34 (56%) patients. Mucositis affected 7 of 34 (21%) patients and was significantly associated with the occurrence of lesions of the oral mucosa at baseline examination; and smaller body surface area--indicating a dose-related toxicity (p less than 0.05). In four of the patients with mucositis (57%) granulocytopenia developed during the 7 days after the onset of mucositis. Intraoral candidiasis affected 4 of 34 (12%) patients.

A prospective cohort study of the orofacial effects of vincristine neurotoxicity.

Neurotoxicity is the dose-limiting side effect of vincristine sulfate. This study was designed to investigate neurotoxicity affecting the head and neck in a population of cancer patients receiving vincristine. Forty patients were given baseline interviews and oral examinations, and these were repeated weekly for the first 7 wk of treatment. Twenty-six patients (65%) developed symptoms of neurotoxicity: orofacial pain, 22/40 (55%); numbness 1/40 (2.5%); paresthesia 4/40 (10%); difficulty with mastication 1/40 (2.5%); involuntary movements 3/40 (7.5%); and voice changes, 4/40 (10%). Most symptoms occurred in the first week except voice changes (hoarseness and weakness) which did not occur until the third week of treatment. Using Fisher's exact test, neurotoxicity affecting the orofacial area was found to be significantly associated with younger age and single marital status indicating that psychosocial factors may affect susceptibility to the neurotoxic effects of vincristine. This prospective cohort study confirms previous anecdotal reports of vincristine neurotoxicity affecting the head and neck.

A prospective study of magnetic resonance imaging in lymphoma staging.

In this prospective study, magnetic resonance imaging (MRI) was compared with computed tomography (CT) in patients with non-Hodgkin's lymphoma (NHDL), and with CT and laparotomy in patients with Hodgkin's disease (HD). Among 31 patients with NHDL, there was agreement between MRI and CT findings in 21 patients; MRI findings were positive and CT findings were negative in 8 patients; and MRI findings were negative and CT findings were positive in 2 patients. The false-negative findings of MRI included a laparotomy-proven mesenteric mass and a 6.6-cm lesion in the spleen, both shown by CT. In 13 evaluable patients with HD, there was agreement between MRI and laparotomy findings in 8 patients; MRI findings were positive and laparotomy findings were negative in 4 patients; and MRI findings were negative and laparotomy findings were positive in 1 patient. CT findings agreed with laparotomy findings in nine patients; CT findings were positive and laparotomy findings were negative in one patient: and CT findings were negative and laparotomy findings were positive in three patients. This suggested that MRI, although more sensitive than CT, was less specific with more false-positive findings. The spin-lattice relaxation time (T1) for the spleen was generally higher in patients with HD who had pathologically confirmed splenic involvement, and tended to increase with increasing spleen weight. This study was performed on a prototype 0.15 Tesla (Technicare Inc., Solon, OH) resistive unit at a time when methods and reporting for MRI were still being developed. Although MRI appears to have fewer false-negative findings than CT in evaluating the abdomen of lymphoma patients, the lack of a gastrointestinal contrast agent and specificity of T1 elevations in the spleen would not suggest that MRI could replace CT or laparotomy as a staging technique.

Levamisole and 5-fluorouracil therapy for resected colon cancer: a new indication.

OBJECTIVE: To evaluate the benefits and risks of postoperative treatment with levamisole plus 5-fluorouracil (5-FU) in patients with colon cancer. DESIGN: Computerized searches of MEDLINE and CANCERLIT were performed, and the reference list of each retrieved article was checked. Only randomized trials of therapy with levamisole alone or combined with 5-FU for colon cancer without distant metastases were included. The studies were then evaluated with the use of four criteria. RESULTS: We reviewed six randomized trials, of which three satisfied our criteria. Two studies demonstrated a significant improvement in the survival rate with levamisole plus 5-FU among patients with colon cancer and pathologically confirmed metastases to adjacent lymph nodes (Dukes' stage C). A subgroup analysis in another study demonstrated a similar benefit. The toxic effects of the drugs were generally mild. The three other studies showed no difference in survival rates between the treatment groups; however, the samples were too small to detect a clinically or statistically important difference. CONCLUSIONS: Because many patients with colon cancer will suffer a relapse we recommend that they be offered the opportunity to participate in clinical trials of adjuvant therapy. For those with stage C disease not entering a clinical trial levamisole plus 5-FU is appropriate adjuvant therapy.

Quality of life in stage II breast cancer: an instrument for clinical trials.

A questionnaire has been developed for use as an outcome measure in clinical trials of adjuvant chemotherapy in women with stage II breast cancer. The selection of items for this Breast Cancer Chemotherapy Questionnaire (BCQ) was based on the problems and experiences felt to be most important by women undergoing adjuvant chemotherapy. The BCQ consists of 30 questions that focus on loss of attractiveness, fatigue, physical symptoms, inconvenience, emotional distress, and feelings of hope and support from others. The BCQ, other instruments that evaluate quality-of-life (Spitzer, Karnofsky, and Rand), and patient and physician global assessments were administered serially to 418 patients taking part in a randomized trial comparing a 12-week regimen and a 36-week regimen of adjuvant chemotherapy. The validity of the BCQ is supported by its correlation with the Rand Emotional (r = .58), Rand Physical (r = .60), and Spitzer (r = .62) questionnaires. The BCQ correlated more strongly with global ratings of both physical and emotional function by the patients and their physicians than the other instruments. A comparison of the quality-of-life outcomes of patients in the two treatment groups in the period beyond 3 months after initiation of treatment, when one group had completed the treatment course and the other was still on treatment, revealed that the BCQ and Karnofsky were the only instruments able to demonstrate differences between the groups (P less than .0001). Hence, the BCQ is a valid and responsive method of assessing treatment-related morbidity in patients receiving adjuvant chemotherapy for stage II breast cancer.