Delayed appearance of carbon granulomas of the scalp after use of carbon fiber pins for refixation of a stereotactic head frame. Case report.

The authors present a case involving the formation of several carbon granulomas in the scalp of a woman 7 years after she underwent craniotomy. Her operation had included the use of carbon fiber pins for refixation of a stereotactic head frame. Carbon granulomas have been noted in multiple organs following surgical or traumatic carbon deposition, but have not been reported in association with neurosurgical carbon fiber pins used for head fixation. The lesions in this case arose a few months after initiation of chemotherapy for the patient's brain tumor. The relationship of carbon and cutaneous granuloma formation to adjuvant therapies and treatment strategies is discussed.

Phase II trial of neoadjuvant estramustine and etoposide plus radical prostatectomy for locally advanced prostate cancer.

OBJECTIVES: To report the results of a Phase II trial of neoadjuvant estramustine and etoposide before radical prostatectomy in patients with locally advanced disease. METHODS: Treatment consisted of three cycles of estramustine (10 mg/kg/day) and etoposide (50 mg/m(2)/day) orally on days 1 through 21, repeated every 28 days, followed by radical prostatectomy. The eligibility criteria included locally advanced prostate cancer (clinical Stage T2b/c or T3, prostate-specific antigen [PSA] level of 15 ng/mL or greater, or Gleason score of 8 or higher) without evidence of metastatic disease. The median PSA level was 14 ng/mL (range 5.3 to 50), the median Gleason score was 7 (range 6 to 9), and 44% had Stage T2b/c or T3 disease. The primary endpoint was feasibility of neoadjuvant therapy and radical prostatectomy, including drug and surgery-related toxicities. Secondary endpoints included the pre-prostatectomy PSA level, local response, pathologic outcomes, and time to PSA failure. RESULTS: Eighteen patients were entered and completed all three cycles of therapy, and 16 (89%) underwent radical prostatectomy. A local response occurred in 15 (94%) of 16 patients with palpable tumors, and the serum PSA reached undetectable levels after therapy and before radical prostatectomy in 9 patients (50%). Five patients (28%) experienced grade 3 toxicity (two with deep venous thrombosis, two with neutropenia, and one with diarrhea) and one (6%) experienced grade 4 toxicity (pulmonary embolus) before surgery. The median operative time was 125 minutes, the mean blood loss was 665 mL, and the mean length of stay was 2.5 nights. Five minor surgical complications occurred in 4 patients. The pathologic analysis demonstrated residual carcinoma with squamous metaplasia and androgen deprivation effect in all patients. Five patients (31%) had organ-confined disease and 9 patients (56%) had specimen-confined disease. All patients achieved an undetectable PSA level postoperatively and at a median follow-up of 14 months (range 5 to 20) and without additional therapy, all 14 patients with negative lymph nodes were disease free. CONCLUSIONS: This trial confirms the feasibility of radical prostatectomy with acceptable surgical morbidity after neoadjuvant therapy with estramustine and etoposide in patients with locally advanced prostate cancer. However, this regimen is associated with estramustine-induced thromboembolic toxicity. The results of the pathologic analysis suggest a higher than expected rate of organ-confined and specimen-confined disease, but little histologic evidence of antitumor effect beyond that associated with androgen deprivation. Additional study of this paradigm with other drug regimens is warranted.

Mature results from a phase II trial of accelerated induction chemoradiotherapy and surgery for poor prognosis stage III non-small-cell lung cancer.

Mature results are reported from a phase II trial of accelerated induction chemoradiotherapy and surgical resection for stage III non-small-cell lung cancer whose prognosis is poor. Surgically staged patients with poor prognosis stage III non-small-cell lung cancer were eligible for this study. Four-day continuous intravenous infusions of cisplatin 20 mg/m2/day, 5-fluorouracil 1,000 mg/m2/day, and etoposide 75 mg/m2/day were given concurrently with accelerated fractionation radiation therapy, 1.5 Gy twice a day, to a total dose of 27 Gy. Surgical resection followed in 4 weeks. Identical postoperative chemotherapy and concurrent radiation to a total dose of 40 to 63 Gy was subsequently given. Between February 1991 and June 1994, 42 eligible and evaluable patients, 23 with stage IIIA disease and 19 with stage IIIB disease, were entered in this trial. Treatment was well tolerated. The pathologic response rate was 40%. This response was complete in 5%. With a median follow-up of 54 months, the Kaplan-Meier 4-year survival estimate is 19%: 26% for stage IIIA and 11% for stage IIIB patients. Patients with a pathologic response, resectable disease, or pathologic downstaging to stage 0, I, or II had a better survival. The 4-year estimates of locoregional and distant disease control are 70% and 19%, respectively. It is concluded that although the ultimate role of concurrent chemoradiotherapy and surgery in stage III non-small-cell lung cancer must await the results of phase III clinical trials, survival and locoregional control in this study appear improved in comparison with historical experience. There is a subset of patients, able to undergo resection with pathologic downstaging, who have a projected survival equivalent to that of patients with more limited disease. Clinical or pathologic tools to identify these patients before treatment would be highly useful.

From serendipity to design: the evolution of drug development in oncology.

Although screening of natural products remains the major method of discovering new anticancer drugs, newer techniques of rational drug design, computer-aided drug design, and combinatorial synthesis promise to broaden the scope of compounds available for screening. Recent changes in Food and Drug Administration rules allow for accelerated approval of drugs for treating cancer and other life-threatening illnesses, although the three-phase process of clinical trials remains largely unchanged.

Successful re-treatment with taxol after major hypersensitivity reactions.

PURPOSE: To describe the successful re-treatment of eight patients who had major hypersensitivity reactions (HSRs) to taxol and to suggest a regimen for re-treating patients who develop major HSRs. PATIENTS AND METHODS: The treatment courses of eight patients who developed major HSRs and were rechallenged with taxol were reviewed. Patients in this report represent all patients who are known to have been rechallenged with taxol after major HSRs. RESULTS: The most common approach used to rechallenge patients consisted of premedication with multiple high doses of corticosteroids and H1- and H2-histamine antagonists followed by the initiation of the taxol infusion at a reduced rate. All patients who experienced major HSRs were rechallenged successfully. After the rechallenge, these patients received 32 additional courses of taxol without HSRs. CONCLUSION: Re-treatment with taxol after major HSRs is feasible using multiple high doses of corticosteroids and antihistamine premedications and a reduced taxol infusion rate under close supervision. This approach may represent a valid alternative to the termination of taxol; however, a prospective evaluation is required to determine the true efficacy of this approach.