Pierre R. Band

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.

L-Phenylalanine Mustard (L-PAM) in the Management of Primary Breast Cancer

Abstract Prolonged L-phenylalanine mustard (L-PAM) administration as an adjuvant to mastectomy in the management of patients with primary breast cancer and pathologically positive axillary nodes was evaluated by a prospective, randomized, clinical trial. Treatment failures occurred in 22 per cent of 108 patients receiving placebo and 9.7 per cent of 103 women given L-PAM (p = 0.01). A statistically significant difference (p = 0.02) existed in favor of L-PAM relative to disease-free interval. In premenopausal women, the difference with respect to disease-free interval of treated and control groups was highly significant (p = 0.008). A treatment failure occurred in 30 per cent of premenopausal patients receiving placebo and 3 per cent of those treated with L-PAM (p = 0.008). Whereas a similar trend was observed in postmenopausal patients, the difference is not statistically significant. Thus, L-PAM has been demonstrated to be effective in the treatment of women with primary breast cancer, particularly those...

Leukemia Following Hodgkin's Disease

To investigate the effect of different treatments for Hodgkins disease on the risk of leukemia, we used an international collaborative group of cancer registries and hospitals to perform a case-control study of 163 cases of leukemia following treatment for Hodgkins disease. For each case patient with leukemia, three matched controls were chosen who had been treated for Hodgkins disease but in whom leukemia did not develop. The use of chemotherapy alone to treat Hodgkins disease was associated with a relative risk of leukemia of 9.0 (95 percent confidence interval, 4.1 to 20) as compared with the use of radiotherapy alone. Patients treated with both had a relative risk of 7.7 (95 percent confidence interval, 3.9 to 15). After treatment with more than six cycles of combinations including procarbazine and mechlorethamine, the risk of leukemia was 14-fold higher than after radiotherapy alone. The use of radiotherapy in combination with chemotherapy did not increase the risk of leukemia above that produced by the use of chemotherapy alone, but there was a dose-related increase in the risk of leukemia in patients who received radiotherapy alone. The peak in the risk of leukemia came about five years after chemotherapy began, and a large excess persisted for at least eight years after it ended. After adjusting for drug regimen, we found that patients who had undergone splenectomy had at least double the risk of leukemia of patients who had not, and an advanced stage of Hodgkins disease carried a somewhat higher risk of leukemia than Stage I disease. We conclude that chemotherapy for Hodgkins disease greatly increases the risk of leukemia and that this increased risk appears to be dose-related and unaffected by concomitant radiotherapy. In addition, the risk is greater for patients with more advanced stages of Hodgkins disease and for those who undergo splenectomy.

Xanthine Nephropathy in a Patient with Lymphosarcoma Treated with Allopurinol

ALLOPURINOL is an agent of proved value for the treatment of hyperuricemic and hyperuricosuric states.1 , 2 Both allopurinol and its principal metabolic product, oxypurinol, inhibit the enzyme xant...

Combination chemotherapy for metastatic breast carcinoma. Prospective comparison of multiple drug therapy with L‐phenylalanine mustard

A prospective randomized clinical trial was undertaken in 184 patients with metastatic breast carcinoma to compare single drug chemotherapy with L‐phenylalanine mustard (L‐PAM) and intermittent combination chemotherapy with cyclophosphamide, methotrexate, and 5‐fluourouracil (CMF). All patients had not been previously treated with cytotoxic drugs and all had objectively measurable visceral or soft tissue disease. Of the 93 patients who received CMF, 49 (53%) achieved a complete (14 patients) or partial (35 patients) regression of measurable tumor, for a median duration of 25 weeks. Eighteen of the 91 patients (20%) treated with L‐PAM responded, for a median duration of 13 weeks. The toxicity was primarily hematologic, and greater in the CMF group, which also received more cycles of therapy because of the higher rate and duration of response. The overall survival of CMF‐treated patients was superior to that of the single drug group. The differences were even greater when the patients were subclassified according to the presence of liver involvement or nonambulatory performance status. The superior antitumor effect of CMF over L‐PAM suggests that it may be a more effective drug regimen to be used as an adjuvant to primary therapy.

Clinical phase I study of the hypoxic cell radiosensitizer RO-07-0582, a 2-nitroimidazole derivative.

RO-07-0582 toxicity studies were performed in 12 patients for a total of 16 assays. Single and multifraction dose schedules were used, and drug concentrations in solid tumor tissue, cerebrospinal fluid, and blood (at 14 to 24 hr.) were established. A severe peripheral neuropathy occurred in 1 patient on the multifraction regimen when the total dosage reached 24 g. Drug absorption and concentration in the blood do not significantly differ from that of metronidazole. Maximum blood levels were reached at from 2 to 4 hr., and several days subsequent to administration had stabilized to levels only slightly above control levels.

Identification of occupational Cancer risks in British Columbia : A population-based case-control study of 995 incident breast Cancer cases by menopausal status, controlling for confounding factors

Lifetime occupational histories as well as information on known and suspected breast cancer risk factors were collected by means of a self-administered questionnaire from 1018 women with incident breast cancer ascertained from the British Columbia Cancer Registry, and from 1020 population controls. A matched case-control study design was used. Conditional logistic regression for matched sets data and the likelihood ratio were used in a two-step procedure and were performed separately for pre-menopausal women, post-menopausal women, and for all cases combined. Excess risk was noted for several white-collar occupations. Significantly increased risk was observed: (1) among pre-menopausal women: in electronic data-processing operators; barbers and hairdressers; in sales and material processing occupations; and in the food, clothing, chemical and transportation industries; (2) among post-menopausal women: in schoolteaching; in medicine, health, and nursing occupations; in laundry and dry-cleaning occupations; and in the aircraft and automotive, including gasoline service station, industries. Several significant associations were also seen in the combined group of pre- and post-menopausal women, particularly in crop farmers and in the fruit and vegetable, publishing and printing, and motor vehicle repair industries. The results of this study suggest excess breast cancer risk in a number of occupations and industries, notably those that entail exposure to solvents and pesticides.

Comparison of induction chemotherapies for metastatic breast cancer. An eastern cooperative oncology group trial

Patients with advanced breast carcinoma and no prior chemotherapy were prospectively evaluated to assess the Induction capabilities of cyclophosphamide, methotrexate and 5‐fluorouracil (CMF), Adriamycin and vincristine (AV), and CMF plus prednisone (CMFP). The crossover responsiveness from CMF or CMFP to AV and of AV to CMF were also assessed. A disproportionate randomization led to 166 analyzable cases on AV, 79 on CMF and 86 on CMFP Induction. One hundred and twelve patients were evaluated on crossover. Induction response rates were similar with 56% on AV, 57% on CMF and 63% on CMFP. Crossover response rates ranged from 32% to 41%. CMFP and AV were superior to CMF in terms of response duration (P = 0.05), and CMFP was superior to either in terms of time to treatment failure (P = 0.04), and survival (P = 0.03). Treatment failures occurred in only the on‐study organ sites of disease in 73% of the patients and did not appear to be related to the response achieved. CMF was associated with more thrombocytopenia than either AV or CMFP (P = 0.03). AV was associated with fewer infections than CMFP (P = 0.02), less diarrhea than CMFP (P = 0.04), more emesis than CMF (P = 0.02), and more neurologic toxicity than either CMF or CMFP (P < 0.0001). There was also more emesis with CMF than with CMFP (P = 0.006). CMFP was associated with greater delivery of CMF than was the CMF regimen despite a similar day 1 leukocyte distribution. These results strongly suggest that CMF(P) and AV are clinically noncross‐resistant regimens, that AV and CMF are essentially equivalently active induction regimens, and that CMFP is superior to CMF and AV.

Assessment of adult cancer pain: shortcomings of current methods.

&NA; The evaluation of cancer pain remains a problematic clinical problem, not only due to the subjective and multidimensional nature of pain per se, but also because of its specific characteristics. Cancer pain has an insidious onset, often involves many sites, and is frequently multicausal. Tools have been developed to quantify pain, the most commonly used being the verbal rating scale (VRS), the visual analogue scale (VAS), and the McGill Pain Questionnaire (MPQ). The first 2 scales are short, easy to administer and to score, but only measure pain intensity. The VRS is assumed to be an ordinal scale although unequal differences between pain descriptors have been demonstrated; it offers a restrictive choice of words that may not represent pain experience with sufficient precision, and is not sensitive to change especially for mild pain. The VAS on the other hand, represents pain as a continuum and is sensitive to change. The MPQ has the advantage of evaluating the sensory, affective and evaluative dimensions of pain. However, it is lengthy to administer and some words are not readily understandable. In addition, the words within a given category are considered to be equidistant, the number of words in each category are unequal, and the number of categories evaluating a given dimension are not taken into account when calculating the total pain rating index. A further issue in assessing pain, other than the choice of a valid and reliable tool, is the frequency with which pain evaluations should be repeated. To date no studies have addressed this problem. The timing of pain assessment has been determined more by convenience than by data related to cancer pain fluctuations. In addition to discussing the difficulties specific to each instrument, suggestions for improving cancer pain evaluation are presented.

Noncontraceptive hormone use and risk of breast cancer.

All British Columbia (Canada) women under 75 years of age who were diagnosed with breast cancer during 1988–89 were asked to complete a postal questionnaire which included detailed information on menopausal estrogen use. Controls were drawn from the Provincial Voters List, matched by five-year age category to the cases. The present analysis consists of 699 cases and 685 controls who were postmenopausal due to natural causes or to a hysterectomy. There was no overall increase in risk of breast cancer associated with ever-use of unopposed estrogen (odds ratio [OR] = 1.0,95 percent confidence interval [CI] = 0.8–1.3). For estrogen use of 10 years or longer, the relative risk [RR] was 1.6 (CI = 1.1–2.5). The risk estimate for current users was somewhat elevated (OR = 1.4, CI = 1.0–2.0). Compared with women who never used hormone preparations, women who had used estrogen plus progestogen had an RR of 1.2 (CI = 0.6–2.2). Our results suggest that ever-use of estrogen, with or without progestogen, does not appreciably increase the risk of breast cancer. However, long-term and recent use of unopposed estrogen may be associated with a moderately increased risk.