Neoadjuvant chemotherapy in the combined modality approach of locally advanced nonmetastatic breast cancer.

We have treated 76 patients with locally advanced breast cancer, 31 with stage IIIA, 41 with stage IIIB, and 4 with stage IV disease, with primary induction chemotherapy including an attempted hormonal synchronization in 70 patients. All were treated to maximum objective clinical response before proceeding to any local therapy. Patients achieving a complete response with a negative repeat biopsy generally received radiation therapy while patients with residual disease, partial response (PR) or no change (NC) status received debulking surgery prior to radiation therapy. Regardless of response to induction chemotherapy, patients received at least 6 additional months of chemotherapy following local therapy. Initial doses of combination chemotherapy were escalated to targeted myelosuppression. The objective response rate to induction chemotherapy was 93% with 49% complete response (CR), 44% PR, and 7% NC. The median numbers of cycles of chemotherapy to achieve a CR, PR, or NC were 5, 3, and 5, respectively. Three patients who currently have PRs are still on chemotherapy with continued tumor regression. Of 37 patients achieving a CR to chemotherapy, 35 were assessed by biopsies to determine pathological evidence of response. Twenty-three of the 37 patients (62%) were proven to be complete responders with negative biopsies. Twenty-four patients have relapsed, 6 with stage IIIA, 16 with stage IIIB, and 2 with stage IV. Five patients have had locoregional relapses alone, 4 locoregional and distant, and 15 distant alone. Median time to progression is 35.9 months for stage IIIA and 34.2 months for stage IIIB. Median survival is 35.3 months for stage IIIB and is indeterminate for stage IIIA. This aggressive primary chemotherapy regimen with hormonal synchronization followed by local therapy appears to provide excellent local control and encouraging early results on systemic disease control.

Long-term follow-up of testicular function following radiation therapy for early-stage Hodgkin's disease.

Seventeen male patients with pathological staged I-IIIA1 Hodgkin's disease were followed prospectively for radiation damage to the testes from low-dose scattered irradiation. During conventionally fractionated radiation therapy, the testicular dose ranged from 6 to 70 cGy. Testicular function was measured in a prospective fashion by repeated analyses (every 6 to 12 months) of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Patients were also followed by serial semen analyses and by a questionnaire on fertility. The follow-up period ranged from 3 to 7 years after completion of radiation therapy. In patients receiving greater than or equal to 20 cGy, there was a dose-dependent increase in serum FSH values following irradiation, with the maximum difference at 6 months compared with pretreatment levels. All patients showed a return to normal FSH values within 12 to 24 months following irradiation. No significant changes in LH and testosterone were observed in this patient group. Eight patients with a normal pretreatment semen analysis provided serial semen samples and two patients showed transient oligospermia with complete recovery by 18 months following treatment. Four patients have fathered normal offspring following radiation therapy. We conclude that low doses (greater than 20 cGy) of scatter irradiation during treatment for Hodgkin's disease can result in transient injury to the seminiferous tubule as manifested by elevations of FSH for 6 to 24 months following treatment. Below 20 cGy, FSH values remained in the normal range. No evidence of Leydig cell injury (using LH and testosterone) was seen in this dose range (up to 70 cGy). Thus, patients with early-stage Hodgkin's disease can be treated with radiation therapy with little to no risk of irreversible testicular injury. Radiation treatment techniques to shield the testes are discussed.

103Pd brachytherapy and external beam irradiation for clinically localized, high-risk prostatic carcinoma.

PURPOSE: To summarize biochemical failure rates and morbidity of external beam irradiation (EBRT) combined with palladium (103Pd) boost for clinically localized high-risk prostate carcinoma. METHODS AND MATERIALS: Seventy-three consecutive patients with stage T2a-T3 prostatic carcinoma were treated from 1991 through 1994. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (71 patients), Gleason score 7-10 (40 patients), prostate specific antigen (PSA) > 15 (32 patients), or elevated prostatic acid phosphatase (PAP) (17 patients). Patients received 41 Gy EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose: 80 Gy). Biochemical failure was defined as a PSA greater than 1.0 ng/ml (normal < 4.0 ng/ml). Patients whose PSA was still decreasing at the last follow-up were censored at that time. Patients whose PSA plateaued at a value greater than 1.0 were scored as failures at the time the PSA first plateaued. RESULTS: The overall, actuarial freedom from biochemical failure at 3 years after treatment was 79%. In Cox proportional hazard multivariate analysis, the strongest predictor of failure was elevated acid phosphatase (p = 0.04), followed by PSA (p = 0.17), Stage (p = 0.23), and Gleason score (p = 0.6). Treatment-related morbidity was usually limited to temporary, RTOG Grade 1-2 urinary symptoms. One patient, who had both a transurethral incision of the prostate (TUIP) and a transurethral resection of the prostate (TURP), developed low-volume urinary incontinence. The actuarial potency rate at 3 years after implantation was 77% for 46 patients who were sexually potent prior to implant. CONCLUSION: Biochemical freedom from failure rates following combined EBRT and 103Pd brachytherapy for clinically localized, high-risk prostate cancer compare favorably with that reported after conventional dose EBRT alone. Morbidity has been acceptable.

Prognostic role of serum prostatic acid phosphatase for 103Pd-based radiation for prostatic carcinoma.

PURPOSE: To establish the prognostic role of serum enzymatic prostatic acid phosphatase (PAP) in patients treated with palladium (103Pd) and supplemental external beam irradiation (EBRT) for clinically localized, high-risk prostate carcinoma. METHODS AND MATERIALS: One hundred twenty-four consecutive patients with Stage T2a-T3 prostatic carcinoma were treated from 1992 through 1995. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (100 patients), Gleason score 7-10 (40 patients), pretreatment prostate specific antigen (PSA) >15 ng/ml (32 patients), or elevated serum PAP (25 patients). Patients received 41 Gy conformal EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose 80 Gy). Biochemical failure was defined as a PSA greater than 1 ng/ml (normal <4 ng/ml). RESULTS: The overall, actuarial freedom from biochemical failure at 4 years after treatment was 79%. In Cox-proportional hazard multivariate analysis, the strongest predictor of failure was elevated pretreatment acid phosphatase (p = 0.02), followed by Gleason score (p = 0.1), and PSA (p = 0.14). CONCLUSION: PAP was the strongest predictor of long-term biochemical failure. It may be a more accurate indicator of micrometastatic disease than PSA, and as such, we suggest that it be reconsidered for general use in radiation-treated patients.

Characterization of ellipticine binding to native calf thymus DNA.

The binding of [14C]ellipticine to native calf thymus DNA was studied using equilibrium dialysis. A Scatchard polt revealed the presence of high-and low-affinity binding sites in DNA, the former having a K of 4.0 X 10(7) M(-1) and an n (saturation limiting of binding) of 0.078 (1mol ellipticine/13 mol of DNA nucleotides). The forces involved in stabilizing the high-affinity binding, which has been equated with intercalative binding, were due to a combination of hydrophobic interactions and hydrogen bonding. Difference spectra of ellipticine in the presence of the polydeoxynucleotides, poly d(A-T) or poly d(G-C), showed that there was no base specificity involved in the high-affinity binding. Ellipticine binding to the low-affinity sites, which has been equated with surface binding, was due primarily to the participation of electrostatic interactions of ellipticine with the anionic phosphate groups on the double helical surface of DNA.

[Behaviour of free radicals in Alzheimer's disease]. / Comportamento dei radicali liberi nella malattia di Alzheimer.

BACKGROUND: The objective of this study is to evaluate the oxidative stress status in patients affected by Alzheimer's disease, considering the role played by the free radicals in the progression and determination of this disease. METHODS: We have studied 13 patients aged between 65 and 84 years and diagnosed with Alzheimer's disease on the basis of Brain CT scan or MRI results, PTEA (uditive mapped slow potential waves), EEG analysis, evaluation questionnaire (MMSE, ADAS), free radicals levels. RESULTS: This study proved the presence of an oxidative stress status in all patients studied, showing an interaction between the disease and oxidative status. A reduction of the free radicals levels after therapy with determinable anti radicals has also been observed. CONCLUSIONS: The existence between Alzheimer's disease and oxidative stress has already been demonstrated. This study is a contribution to this orientation. Further studies are suggested on the preventive effects, but particularly to demonstrate if the use of antioxidants may be able to decrease or stop the evolution of this disease.

Adjuvant radiotherapy on older and oldest elderly rectal cancer patients.

The purpose of this study was to evaluate the impact of radiotherapy in terms of feasibility and activity in the patients aged > or = 75 with advanced rectal cancer. From January 2002 to December 2006, 41 consecutive patients (27 men and 14 women) aged > or = 75 received radiotherapy for local advanced rectal cancer, 9 in a pre-operative and 22 in a post-operative setting. Sixteen patients received concomitant chemotherapy. Variables considered were age, co-morbidities, evaluated according to the adult co-morbidity evaluation index (ACE-27), surgery versus no surgery, and timing of radiotherapy. The median age was 80.5 years (range 75-90). A total of 19.5% of the patients had no co-morbidity, 48.8% mild, 17.1% moderate, and 14.6% had severe co-morbidities. Thirty-nine subjects (95.1%) were submitted to surgery. All patients but one completed the planned radiation schedule. At a median follow-up of 23.1 months, the 2- and 4-year overall survival rates were 71.8% and 61.6%, respectively. There was a better survival for patients with no or mild co-morbidities (p=0.002) and a good performance status (p=0.003). The cancer-free survival at 2 and 4 years was 78.9% and 26.4%, respectively. No difference in acute and late toxicity rates was found between patients with different ACE-27 indexes. We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients. Patients with no or mild co-morbidities have a significantly better survival. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with adjuvant radiotherapy. Further prospective trials are needed to confirm these results.

Effect of a calcium antagonist, nifedipine, in exercise-induced asthma.

The nifedipine effect was studied in 8 extrinsic asthmatic subjects with exercise-induced asthma. Before the exercise the patients received, in a randomized double-blind manner, either 20 mg nifedipine, sublingually or sodium cromoglycate by inhalation on 2 separate days. Nifedipine and sodium cromoglycate in all patients inhibited the exercise fall in FEV1. No differences were found between the two drugs. Nifedipine is a potent antagonist of calcium ion influx in smooth muscle and secretory cells, and these studies suggest that it may inhibit release of mast cell mediators and reduce bronchial smooth muscle contractility in asthma.

Treatment of locally advanced breast cancer using primary induction chemotherapy with hormonal synchronization followed by radiation therapy with or without debulking surgery.

Fifty-one patients with stage IIIA or IIIB locally advanced breast cancer received primary induction chemotherapy (hormonal synchronization, 46 patients) to a maximum objective clinical response before proceeding to local therapy. Patients achieving a pathological complete response (CR) received radiation therapy, while patients with residual disease, partial response (PR), or stable disease (NC) received debulking surgery prior to radiation therapy; in all patients, 6 additional months of chemotherapy were administered. Chemotherapy consisted of cyclophosphamide (500 mg/m2 iv) and doxorubicin (30 mg/m2 iv) on day 1; tamoxifen (40 mg/m2 orally) on days 2-6; Premarin (0.625 mg/m2 orally) every 12 hours for three doses, beginning on day 7; and methotrexate (300 mg/m2 iv) followed in 1 hour by 5-fluorouracil (500 mg/m2 iv) on day 8 and leucovorin rescue (10 mg/m2 orally) every 6 hours for six doses, beginning 24 hours after methotrexate. Fifty patients are evaluable with respect to response, time to disease progression, and survival. The rate of objective response to chemotherapy was 90%; 52% of the patients had CR, 38% had PR, and 10% had NC. The median numbers of chemotherapy cycles to achieve CR, PR, and NC were five, four, and four, respectively. Twenty-four patients with CR to chemotherapy were pathologically assessed, 22 by multiple biopsies and 2 by mastectomy. Seventy-one percent of the patients were proven to have pathological CR. All patients completing combined therapy thus far are disease free. Nine of 29 patients with stage IIIB disease have relapsed; 7 of 23 with inflammatory histology have relapsed; and 2 of 20 with stage IIIA disease have relapsed.(ABSTRACT TRUNCATED AT 250 WORDS)