Severe systemic reaction to diphosphonate bone imaging agents: skin testing to predict allergic response and a safe alternative agent.

We describe a severe systemic reaction which occurred in a patient on two occasions after i.v. injection of chemically related diphosphonate bone imaging agents. Skin testing showed reactivity to multiple commercially available diphosphonate compounds but no significant response to pyrophosphates. A subsequent pyrophosphate bone scan resulted in no adverse reaction. Severe systemic reactions to diphosphonates can occur, skin testing may prove useful in evaluating allergic reactions, and pyrophosphates appear to be a safe alternative agent in patients proven or suspected allergic to diphosphonates.

Combined modality therapy for first recurrence of breast cancer. A Southwest Oncology Group study.

The Southwest Oncology Group has completed a study of 213 women with the first recurrence of breast cancer. Eligibility included a radical or modified radical mastectomy for cure and recurrence which had received no other form of therapy. Patients were started on tamoxifen (TAM) 20 mg daily (Phase I). Failures, or responders who subsequently failed, had an oophorectomy if the ovaries were intact, and TAM was continued (Phase II). During Phase III, eligible patients underwent an adrenalectomy, and lastly, in Phase IV, patients received chemotherapy. Responses to TAM were seen in 40% of 56 premenopausal patients, 46% of 95 postmenopausal women, and 44% of 62 patients without intact ovaries. Oophorectomy plus TAM gave responses only in premenopausal women who failed to respond on TAM or in postmenopausal patients who had a prior response to TAM. Adrenalectomy was successful in 7 of 21 patients. Chemotherapy resulted in 13% complete and 47% partial responses. Median overall survival was 108, 155, and 115 weeks, respectively, for the three patient groups. The authors believe that until results with chemotherapy improve significantly, hormonal therapy is the preferred first-line management of recurrent breast cancer.

Clinical correlations of leukemic clonogenic cell chemosensitivity assessed by in vitro continuous exposure to drugs.

This study was performed to assess the value of prolonged, as opposed to short-pulse, in vitro exposure of leukemic cells to chemotherapeutic drugs in leukemic clonogenic assay for prediction of clinical response. In 21 patients with acute nonlymphocytic leukemia treated with intensive combination chemotherapy based on an anthracycline and 1-beta-D-arabinofuranosylcytosine infusion, chemotherapy sensitivity of leukemic clonogenic cells was assessed in comparison with that of normal myeloid clonogenic cells by the in vitro continuous exposure to drugs throughout the entire culture period. Analysis of these in vitro data in terms of prediction of achieving clinical complete remission was carried out in comparison with data on 22 cases in which in vitro sensitivity was assessed by the pulse 1-hr exposure. The in vitro sensitivity index, expressed as a log odds ratio, was positive (greater than 0) in 8 of 11 patients achieving complete remission and negative (less than 0) in 7 of 10 patients failing to achieve complete remission, with an overall correlation of 71%. This is at least as good as the pulse exposure method, which has a correlation of 68%. If sensitivity indexes of marginal magnitudes (--1.0 approximately +1.0) are excluded, the correlation increases to 92% (12 of 13 patients). The correlation appears to improve especially for 1-beta-D-arabinofuranosylcytosine by the continuous exposure method (71%) as compared with the pulse method (57%). This study establishes the feasibility of an in vitro chemotherapy sensitivity testing of leukemic clonogenic cells by continuous in vitro drug exposure and suggests that the continuous exposure method may be better than the pulse method for antimetabolites such as 1-beta-D-arabinofuranosylcytosine. The data also suggest that simulation of the in vivo drug schedule may be important in this in vitro test.

Chemotherapy sensitivity assessment of leukemic colony-forming cells with in vitro simultaneous exposure to multiple drugs: clinical correlations in acute nonlymphocytic leukemia.

For 13 patients with acute nonlymphocytic leukemia receiving four-drug combination chemotherapy (14 chemotherapy trials), leukemic bone marrow cells were obtained before treatment and were exposed in vitro to all four-drug-mixture solutions simultaneously followed by the survival assessment of leukemic colony-forming cells (L-CFU). Survival of normal marrow colony-forming cells (CFU-C) was also assessed concurrently, and the sensitivity index (SI) of leukemic cells was determined as the ratio of the survival of CFU-C to that of L-CFU. Correlations of in vitro results to clinical results were excellent: four of five trials resulting in complete remission had high SI and eight of nine trials without complete remission had low SI (P = 0.02). The potential advantages of this method of exposing cells to drug mixture are discussed in terms of detecting drug synergism and improving the efficiency of in vitro chemotherapy sensitivity studies.

Adriamycin in combination for the treatment of breast cancer: a Southwest Oncology Group study.

Patients with advanced breast cancer who had not previously received chemotherapy were treated on a three-arm prospective study: adriamycin day 1 plus 5-FU on day 1 and 8 (AF), adriamycin day 1, plus 5-FU day 1 and 8, and cyclophosphamide day 1 (AFC), and adriamycin day 1 plus 5-FU day 1 and 8, cyclophosphamide day 1 and methotrexate day 1 (AFCM). These courses were repeated every 21 days. The response rate was 44/105 (42%) AF, 44/103 (43%) AFC and 52/105 (49%) AFCM. The length of response was 22, 33 and 35 weeks, respectively, for AF, AFC and AFCM (P = 0.21). The median survival, 64 weeks, was equal in all three limbs. The major toxicity was leukopenia. Twenty-eight percent developed a WBC of less than 2,000/microliter, which resulted in seven deaths (2.2%).