The spectrum of vascular lesions in the mammary skin, including angiosarcoma, after breast conservation treatment for breast cancer.

BACKGROUND: With the general acceptance of lumpectomy, axillary staging, and radiotherapy as local treatment for infiltrating breast cancer, an appreciation is evolving for the spectrum of vascular lesions that occur in the mammary skin after this treatment. Most of these lesions develop within the prior radiation field after breast conservation treatment. STUDY DESIGN: A retrospective chart and slide review was conducted, consisting of five patients with cutaneous vascular lesions after breast conservation treatment for infiltrating breast cancer. RESULTS: The latent time interval from definitive treatment of breast cancer to the clinical recognition of vascular lesions ranged from 5 to 11 years. Two patients did not have either arm or breast edema, two patients had breast edema, and the fifth patient had arm edema. Lesions arising in the irradiated mammary skin included extensive lymphangiectasia (one), atypical vascular lesions (two), and cutaneous angiosarcoma (four). CONCLUSIONS: Atypical vascular lesions at the skin margins of mastectomy may be predictive of recurrence after resection of angiosarcoma. Excision of skin from the entire radiation field may be necessary to secure local control of the chest wall in patients with cutaneous angiosarcoma after therapeutic breast radiotherapy.

Phase II evaluation of menogaril in advanced prostate cancer: Eastern Cooperative Oncology Group EST P-A885.

Menogaril is a semisynthetic anthracycline that is less cardiotoxic than doxorubicin in a preclinical model. We conducted a phase II trial to determine the activity of menogaril in hormone-refractory prostate cancer. Between October 1985 and November 1987, 32 eligible patients were enrolled and were divided into good- and poor-risk categories, the latter being defined by prior radiotherapy to less than one third of the marrow-containing skeleton. Good-risk patients received a starting dose of 200 mg/m2 by 60-minute IV infusion, whereas the poor-risk patients received 160 mg/m2. Treatment was repeated every 3 weeks until disease progression. Menogaril caused leukopenia in 90% of patients, of whom 47% had grade III or IV toxicity. Thrombocytopenia was uncommon and mild, with only three patients (9%) experiencing grade II toxicity. Nonhematologic toxicity included mucositis (9%), and mild weight loss in 33% of patients. Nine patients (28%) had stable disease of 3 or more months' duration. There were no objective partial or complete responses. The median time to progression for the entire group was 10 weeks, and the median survival time for all patients was 24 weeks. Because of appreciable toxicity and limited antitumor activity, further study of menogaril cannot be recommended in hormone-refractory prostate cancer.

A method for the quantitative analysis of human heat shock gene expression using a multiplex RT-PCR assay.

A quantitative multiplex RT-PCR assay is described to measure the levels of messenger RNAs for eight human genes encoding the heat shock proteins (HSP) and molecular chaperones hsp90alpha, hsp90beta, hsp70, hsc70, mtHsp75, Grp78 (BiP), hsp60 and hsp27. The basis of this assay is reverse transcription of total RNA isolated from human cells followed by amplification with PCR. By the careful selection of pairs of oligonucleotide primers corresponding to unique regions of each heat shock gene, selectivity can be attained such that messenger RNAs of multiple heat shock genes can be analyzed simultaneously in a single reaction. This method provides both the absolute and relative levels of each heat shock message by including in the reaction, reference control RNAs corresponding to in vitro transcripts of heat shock gene plasmids carrying small internal deletions.

Paclitaxel as the initial treatment of multiple myeloma: an Eastern Cooperative Oncology Group Study (E1A93).

The authors assess the activity and toxicity of paclitaxel in previously untreated patients with multiple myeloma. Eighteen patients with previously untreated multiple myeloma were enrolled. Paclitaxel was given in a dose of 250 mg/m2 by a continuous intravenous infusion for 24 hours every 21 days for four cycles. All patients received granulocyte colony stimulating factor in a dose of 5 microg/kg each day until the absolute neutrophil count was 10,000/mm3. All patients were evaluated after four cycles. Four (29%) objective responses were observed in the 14 eligible patients. No complete responses occurred. Three lethal toxicities were observed, two were the result of neutropenic sepsis. Sixty-one percent of patients experienced some type of severe nonhematologic toxicity. Patients who received four cycles of paclitaxel were given further treatment at the discretion of the investigator. The median survival of all eligible patients was 2.8 years, which is comparable with the median survival with melphalan and prednisone of 2.3 years or vincristine, carmustine, melphalan, cylophosphamide, and prednisone of 2.4 years. Paclitaxel in the dosage used in this study has prohibitive toxicity. The four (29%) responses in 14 evaluable untreated patients indicates that paclitaxel is active in the treatment of multiple myeloma. No complete remissions were recorded. Further studies using paclitaxel in a smaller dose, in combination with other agents, or using one of the paclitaxel analogs may be useful in the treatment of multiple myeloma.

Recommendations on follow-up of breast cancer patients following primary therapy.

Follow-up of breast cancer patients who have completed their primary therapy has not been standardized. The literature is reviewed and it is proposed that "minimal" follow-up with history and physical examination is the most appropriate procedure. Data show that more expensive imaging studies be carried out only in patients who are symptomatic from their disease, otherwise such an intensive follow-up schedule is not cost effective.

Parietal pleurectomy for malignant pleural effusion.

BACKGROUND: Malignant pleural effusions are seen frequently in clinical practice and are most commonly caused by breast cancer and lung cancer. Standard treatment usually consists of complete drainage of the pleural space via a chest tube and instillation of a pleural irritant to obtain pleural symphysis. In a majority of instances, such treatment effectively controls the pleural space; however, standard treatment fails in some cases. METHODS: Twenty-four patients who did not respond to standard treatment for malignant pleural effusion were subjects for parietal pleurectomy, which was usually performed through an axillary thoracotomy. In several cases, decortication was also necessary. The study population was composed of 18 women and six men. Twelve of the patients had carcinoma of the breast, five carcinoma of the lung, and four carcinoma of the ovary. RESULTS: Three patients died in the perioperative period to give an operative mortality of 12.5%. The other 21 patients all had satisfactory control of their recurrent malignant effusions. Their survival time ranged from 2 to 30 months (average 10.6). CONCLUSIONS: Parietal pleurectomy is an effective operation for recurrent malignant pleural effusion. However, because of its significant morbidity and mortality, it should be reserved for failures of standard treatment, and patient selection is important.

High-dose aminothiadiazole in advanced colorectal cancer. An Illinois Cancer Center phase II trial.

Thirty-three patients with advanced colorectal carcinoma were entered on a phase II trial of weekly IV aminothiadiazole (175 mg/m2 escalated to 200 mg/m2) with concomitant allopurinol and non-steroidal anti-inflammatory agents (NSAID's). Toxicity was predominantly GI, cutaneous, and chest pain/dyspnea. Twenty-five percent of patients had grade 3 or 4 toxicity. There were no responses in 27 evaluable patients. Median survival was 12 months. Aminothiadiazole, at higher doses than used in previous reports, when given with NSAID's, had no significant activity against large bowel cancer.

Adherence to a dietary fat intake reduction program in postmenopausal women receiving therapy for early breast cancer. The Women's Intervention Nutrition Study.

PURPOSE: To evaluate the feasibility of integrating a program based on dietary fat intake reduction into adjuvant treatment strategies for postmenopausal women receiving therapy for early breast cancer. PATIENTS AND METHODS: Two hundred ninety postmenopausal women with localized (stage I to IIIa) breast cancer receiving conventional systemic therapy provided informed consent and were randomized in a multicenter trial to either a dietary intervention group receiving a program of individualized instruction for reducing total fat intake or a dietary control group with minimal dietary counseling. RESULTS: Significantly reduced (P < .001) fat intake (in terms of percent calories derived from fat) was observed in the intervention group versus the control group at 3 months (20.3% +/- 2.4% v 31.5% +/- 2.6%, mean +/- SD, respectively) and maintained throughout 24 months of observation. The 50% reduction in daily fat-gram intake (from 66 +/- 23 to 33 +/- 14 g, P < .001) seen at 6 months was associated with reduced saturated fat, monounsaturated fat, polyunsaturated fat, and linoleic acid (P < .001). Significantly lower body weight was also seen in intervention compared with control patients at all observation periods, resulting in a 3.3-kg weight difference 18 months after randomization (P < .001). CONCLUSION: Substantial and sustained dietary fat reduction with associated weight change can be achieved at relatively low cost within the context of conventional multimodality clinical management of postmenopausal women with localized breast cancer. This result supports the feasibility of conducting a full-scale evaluation of the influence of dietary fat intake reduction on the clinical outcome of breast cancer patients.

Extragonadal seminoma involving urinary bladder and arising in the prostate.

The authors report the first instance of a patient with seminoma probably arising from the prostate but also involving the bladder. A 58-year-old man presented with symptoms and signs of prostatic enlargement. Cystoscopy revealed a fungating neoplasm, probably arising from the prostate and surrounding the bladder neck. The biopsy was consistent with the diagnosis of seminoma. The patient experienced complete remission after chemotherapy with bleomycin, cisplatin, and etoposide.

Achieving local control for inflammatory carcinoma of the breast.

A single institution, retrospective study of 28 patients with inflammatory carcinoma of the breast treated from 1984 to 1990 was performed. Patients received two to four cycles of cyclophosphamide, doxorubicin and 5-fluorouracil (CDF) and were then evaluated for mastectomy. Mastectomy was accomplished in 26 patients after CDF. In 21 patients, the breast was resectable after the initial doses of chemotherapy and modified radical mastectomy was done. Radiation therapy was given to 16 of the 21 patients after six to nine cycles of postoperative chemotherapy. The remaining five of 26 patients had a marginal response to CDF and underwent preoperative radiation therapy. Local recurrence occurred in four of five patients receiving preoperative radiation, in three of 16 receiving postoperative radiation and in one of five receiving mastectomy without radiation therapy. The overall observed five year survival rate was 18 percent, with a median of 34 months. Neither dermal lymphatic invasion nor estrogen receptor status were statistically significant variables when analyzing patients for local recurrence or survival. Despite poor long term survival results, the combination of induction CDF, mastectomy and postoperative radiation achieved local control in 81 percent of patients.

A phase II study of mitoguazone and vinblastine in advanced transitional cell carcinoma of the urinary tract.

This is a comparative study to evaluate response rate to mitoguazone (MGBG) and vinblastine (VLB) in 52 evaluable patients with advanced transitional cell carcinoma of the urinary tract. Of 38 patients with measurable disease, two of 18 (11%) on MGBG had partial remission (95% confidence interval: 0.01, 0.35), whereas four of 20 (20%) responded on the VLB arm (95% confidence level: 0.06-0.44). Both responses on the MGBG arm were seen in patients given prior chemotherapy. Side effects of both drugs were significant, with 46% of patients given VLB developing severe or life-threatening hematologic toxicity. Data indicate that both drugs, as single agents, are probably inferior to cisplatin for control of advanced transitional cell carcinoma of the urinary tract.

Phase II trial of continuous drug infusions in advanced ovarian carcinoma: acivicin versus vinblastine.

Sixty-six women with advanced ovarian carcinoma of coelomic epithelial origin were randomly assigned to one of two intravenous single-agent infusion treatment regimens, either acivicin (60 mg/m2/course, administered as a 72-hr infusion) or vinblastine (7.5 mg/m2/course, administered as a 120-hr infusion) every three weeks. All had progressive disease after one to three prior chemotherapeutic regimens. Of 62 patients who were evaluable for response, survival and toxicity, there was one partial response (2%) produced by vinblastine. Median survival was 13 weeks on either treatment arm. Three patients (10%) on the acivicin arm experienced life-threatening myelosuppression. Severe toxicities resulting from this treatment included myelosuppression (26%), neurotoxicity (16%), mucositis (3%) and vomiting (6%). Vinblastine was associated with one lethal pneumonia and five cases of life-threatening myelosuppression (16%); severe toxicities included myelosuppression (58%), genitourinary toxicity (6%), infection (3%), and edema (3%). Neither regimen produces useful clinical results in patients who have relapsed after prior chemotherapy for ovarian carcinoma.

Phase II diaziquone-based chemotherapy trials in patients with anaplastic supratentorial astrocytic neoplasms.

We treated 103 patients with histologically confirmed anaplastic supratentorial astrocytic neoplasms with either diaziquone (AZQ) and carmustine (BCNU) or AZQ and procarbazine. There were 74 patients with glioblastoma multiforme (GBM) and 29 patients with anaplastic astrocytoma (AA). AZQ plus BCNU produced partial (PR) or unequivocal responses in seven of 32 (21.9%) patients with GBMs and three of ten (30%) patients with AAs. Two patients with GBMs (6.3%) and five patients with AAs (50%) showed stable disease (SD). AZQ plus procarbazine produced PRs or unequivocal responses in five of 42 (11.9%) patients with GBMs and nine of 19 (47.4%) patients with AAs. Eight patients with GBMs (19%) and one patient with an AA (5.2%) showed SD. In addition to histologic diagnosis, only the Karnofsky performance-status (KPS) rating independently influenced response and survival. Differences in response rates between the two regimens were not significant, although estimated median survival after adjusting for performance status was slightly better with AZQ plus BCNU than with AZQ plus procarbazine (P = .031). Neither age nor prior chemotherapy were significant independent risk factors. Toxicity was mild and primarily hematologic. We conclude that these AZQ-based regimens have activity in patients with recurrent anaplastic gliomas, but that they are not clearly superior to other agents in current use. The histologic diagnosis of GBM is associated with a significantly worse prognosis than AA, and we believe that this important distinction must be recognized in phase II as well as phase III trials.

Enhanced therapeutic efficacy of cisplatin by combination with diethyldithiocarbamate and hyperthermia in a mouse model.

A spontaneously metastasizing solid tumor model derived by transplanting the TA3Ha murine mammary carcinoma into the s.c. tail tissue of mice was used to develop a treatment strategy for enhancing the therapeutic efficacy of cisplatin (CDDP). This strategy was based on the findings that diethyldithiocarbamate (DDTC) reduces the toxicity of CDDP, and that localized hyperthermia (HT) augments the antitumor efficacy of CDDP. DDTC (500 mg/kg) reduced the CDDP-induced nephrotoxicity and gastrointestinal toxicity as well as increased the CDDP LD10 from 8 to 20 mg/kg in strain A mice. When CDDP and DDTC were used in multiple treatment schedules at 5-day intervals, DDTC protected the hosts but not the tumors against the toxicity of CDDP. HT administered locally to the tumor 1 h after the injection of CDDP (8 mg/kg) in 1 ml Hanks' balanced salt solution increased the antitumor effect but not the host toxicity. While administration of 8 mg/kg CDDP alone or with HT three times at 5-day intervals caused 100% host mortality, this dose of CDDP could be used with no mortality by combining it with DDTC. A combination of 8 mg/kg CDDP with DDTC (750 mg/kg) and HT (43 degree C for 60 min), administered three times at 5-day intervals, retarded the local tumor growth significantly compared to the untreated, CDDP plus DDTC plus HT control groups of mice. The frequency of lung metastasis in these groups on day 30 of tumor inoculation were 0, 90, 90, and 80%, respectively. The mean survival days of the mice treated with CDDP plus DDTC plus HT was 61 +/- 6 compared to 34 +/- 5 in the controls. The results presented here demonstrate that by combining CDDP with DDTC, high doses of CDDP can be safely administered. When localized HT is combined with high dose CDDP and DDTC, the tumor growth retardation and the host survival prolongation are significantly better than those obtained with the highest tolerable dose of CDDP alone or CDDP plus HT.