The paper retrospectively reviews the modalities and the long-term results of treatment of 200 consecutive patients with pure seminoma and of 125 patients with testicular carcinomas admitted to the Istituto Nazionale per lo Studio e la Cura dei Tumori of Milan from 1929 to Jan 1973. Radical orchiectomy with high ligation of the spermatic cord at the internal inguinal ring was performed in all previously untreated patients. Those who had had a scrotal operation performed elsewhere were radically reoperated upon. Lymphography and cobalt 60 telecurietherapy were introduced in 1960 and new treatment plans were employed for the irradiation of the deep lymphnodes. Since 1968 all operable carcinomas have undergone bilateral retroperitoneal lymphadenectomy and since 1964 all patients with advanced disease have been treated with chemotherapy (single agent or combination). Survival rates were calculated by the actuarial method. The new treatment modalities proved to be significantly superior to the old ones. In pure seminoma a 92% cure rate was obtained in NO patients after prophylactic irradiation of retroperitoneal nodes (2,500-3,000 rad in 3 weeks). In NI-3 patients the cure rate was as high as 75% after radical irradiation of retroperitoneal nodes (3,500-4,000 rad in 4 weeks) as well as prophylactic irradiation of mediastinum and both supraclavicular fossae. Extended radical radiotherapy (combined with chemotherapy in some patients) cured 2/6 N4 and 3/8 M1 patients. According to the old modalities of treatment, figures were respectively 72% in NO cases, 40% in N1-3 and 0% in N4 and M1 patients. In carcinomas, the cure rate after retroperitoneal lymphadenectomy was 91% in N--patients and 47% in N+ cases. In N+ patients post-operative radiation was also performed (4,000-5,000 rad in 5 weeks). After radiotherapy alone (without lymphadenectomy) the rates were 62% in NO and 28% in N1-2 patients. In primary inoperable patients (N3-4 and M1) chemotherapy, with or without radiation, significantly prolonged the survival rate. It is concluded that radiotherapy is the treatment of choice for pure seminoma and in N4 and M1 cases a full course of chemotherapy must be combined with extensive irradiation. Retroperitoneal lymphadenectomy is mandatory in all operable cases of testicular carcinoma while adjuvant chemotherapy may further improve the prognosis in N+ cases. For inoperable carcinomas chemotherapy (plus radiotherapy) is the treatment of choice. The new multiple drug regimens are providing encouraging results.

Adolescent↗

PubMedDate not supplied

Adriamycin plus bleomycin versus cyclophosphamide plus vincristine in advanced carcinoma of the uterine cervix.

The paper reports the results of a prospective controlled study with two drug combinations (adriamycin plus bleomycin versus cyclophosphamide plus vincristine) in 34 consecutive patients with advanced or recurrent carcinoma of uterine cervix. Despite adequate dosage, the incidence of complete and partial remission was low (10% vs 20%) and not superior to that usually obtained with single agent chemotherapy. By adding objective improvement, the over all response rate was 47% and 26%, respectively. The duration of complete plus partial remission was 7.5 and 7.2 months, the median survival for responders 19 and 8.3 months, respectively. After cross over, adriamycin plus bleomycin yielded response in 4/10 patients, cyclophosphamide plus vincristine objective improvement in 1/3 patients. Since the control of advanced cervical carcinoma remains difficult, a combined modality approach with radiotherapy plus adjuvant chemotherapy for stages IIB and III appears worth of trial.

Aged↗

PubMedDate not supplied

Controlled study with 1-phenylalanine mustard (l-PAM) and 5-fluorouracil (5-FU) plus or minus prednisone in advanced breast cancer.

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Breast Neoplasms↗

PubMedDate not supplied

[Controlled pilot study with combination chemotherapy in testicular carcinomas (author's transl)].

In 24 previously untreated patients with advanced testicular carcinoma, the combination of adriamycin, vincristine and methotrexate (AVM) was tested in a prospective randomized study against a combination of non-cross resistant drugs including vinblastine, bleomycin and mithramycin (VBM). Complete and partial (greater than 50%) remission was observed in 4 out of 13 patients treated with AVM and in 3 out of 11 given VBM. In one patient receiving AVM and in two patients treated with VBM, the response at the level of previous inoperable retroperitoneal metastatic lymph nodes allowed a subsequent radical lymph node dissection. After cross-over a partial response for 6 months was obtained in only one patient treated with VBM while none was observed in 4 patients receiving AVM. Both combinations were well tolerated. However, their therapeutic activity seems to be definitely lower with respect to treatment with vinblastine followed by continuous infusion with bleomycin.

Antineoplastic Agents↗

PubMedDate not supplied

Ten years experience with Ewing's sarcoma.

The series comprises 57 consecutive patients with Ewing's sarcoma admitted to the National Cancer Institute of Milan from 1965 to 1976. In 75% the diseas was confined to one bone, while in 25% multiple bone and/or visceral lesions were present. Patients with clinically localized tumor treated before 1971 with local therapy, showed a median disease-free survival of 5 months. After 1971, radiotherapy and/or surgery to local tumor was combined with multiple drug chemotherapy (ADM, VCR, CTX) and the projected median disease-free survival increased to 24+ months. In previously untreated patients with advanced tumor adriamycin, used as single drug, achieved an overall response rate of 73%. This is comparable to that achieved by a new combination including ADM, VCR, CTX, CCNU (75%). This multiple drug regimen is, however, expected to prolong the duration of response.

Adolescent↗

PubMedDate not supplied

Primary chemotherapy in surgically resectable breast cancer.

We have reviewed the current status of primary chemotherapy for resectable breast cancer in view of the possibility that it may improve on results of present adjuvant drug therapies. The observed kinetic acceleration of micrometastases following noncurative surgical excision in animal studies represents strong biologic evidence supporting primary chemotherapy. From a clinical perspective, primary chemotherapy has consistently reduced the frequency of mastectomy in women with tumors initially considered too large for breast-conserving surgery. From studies of various drug combinations, it appears that the incidence of pathologic complete remission usually remains less than 10 percent. Based on results from the Milan study, it appears that the degree of tumor response is a marker of treatment outcome, at least for the first five years. A higher complete-remission rate could be expected by combining doxorubicin with paclitaxel, as has already been observed in the treatment of clinically disseminated breast cancer. In spite of the logical and scientific rationale, the available data do not as yet provide sufficient evidence to indicate a clear superiority of primary chemotherapy over adjuvant chemotherapy. The real question to answer through prospective, randomized trials is not whether the shift from adjuvant to neoadjuvant chemotherapy will result in a superior outcome, but rather how to properly integrate effective primary and adjuvant drug regimens to maximize tumor cell kill. This strategy should be further tested in patients at high risk for occult axillary adenopathy and/or distant micrometastases (i.e., tumor size larger than 2 to 3 cm). However, a more-refined risk assessment approach (e.g., using tumor grade or proliferative index) will clearly be needed. The new treatment approach may also allow for a wider use of fine-needle aspiration biopsy to obtain the primary diagnosis of cancer, a more uniform adoption of breast-conserving surgery, and use of response to chemotherapy as a marker of treatment outcome.

Antineoplastic Agents↗

PubMedDate not supplied

[Primary chemotherapy in operable breast carcinoma].

We have reviewed the current status of primary chemotherapy for resectable breast cancer. Available findings indicate that the most immediate benefit of this treatment approach consists in an important tumor shrinkage, enabling to significantly increase the rates of breast conserving approaches. In spite of the logical and scientific rationale, available data from prospective randomized studies do not provide evidence of a clear superiority of primary chemotherapy over adjuvant chemotherapy. Nevertheless, the observed kinetic acceleration of micrometastases following noncurative surgical excision in animal studies represents a strong biologic evidence supporting primary chemotherapy. From a clinical perspective, primary chemotherapy with conventional regimens can induce a low to moderate rate of pathological complete remissions that appear to be an important marker of favorable treatment outcome. For this reason, well designed, prospectively randomized, large trials with drug regimens more effective than those used so far are mandatory to demonstrate the real worthiness of this newer treatment approach and to define the optimal timing of surgery and other locoregional modalities in respect to the long-term treatment outcome. Should there be no benefit to the use of primary drug treatment, then the biologic consequences of primary tumor removal, as observed in experimental models, are not likely to be of clinical significance. Nonetheless, since primary chemotherapy can achieve long-term results similar to those obtained with postoperative drug treatment while increasing the frequency of breast-sparing approaches, women can be offered a choice to maintain their body integrity. Should improved pathological complete remission rates from more effective regimens of primary chemotherapy translate into improved survival compared with the classical postoperative modality, then, regardless of the tumor diameter at diagnosis, our overall strategy for the management of operable breast cancer will require a radical departure from the traditional dogma.

Animals↗

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Long-term results of an intensive regimen: VEBEP plus involved-field radiotherapy in advanced Hodgkin's disease.

PURPOSE: This pilot study was conducted to evaluate the efficacy and toxicity of a new intensive drug regimen, combined with involved-nodal-field radiotherapy, in advanced Hodgkin's disease not treated by chemotherapy. PATIENTS AND METHODS: From September 1990 to March 1993, 73 evaluable patients with newly diagnosed stage IIB, III (A and B), and IV (A and B) Hodgkin's disease or who were relapsing after primary subtotal or total nodal irradiation were treated with eight cycles of etoposide, epirubicin, bleomycin, cyclophosphamide, and prednisolone (VEBEP) followed by radiotherapy (30-36 Gy) to the nodal site or sites of pretreatment disease. The median duration of follow-up was 68 months. RESULTS: The complete remission rate was 94% (95% CI: 86-98). At 6 years, freedom from progression and overall survival rates were 78% (95% CI: 68-88) and 82% (95% CI: 73-91), respectively. There was one episode of fatal sepsis after bone marrow aplasia that occurred after VEBEP and extended-field irradiation. Hematologic toxicity during chemotherapy was acceptable; without the support of growth factors, grade IV leukopenia and grade IV neutropenia, as determined within cycles, occurred in 38% and 85% of patients, respectively, but was reversible in the vast majority of patients by the day of treatment recycle. No episodes of epidoxorubicin-related cardiomyopathy or symptomatic pulmonary toxicity were documented. Overt and/or subclinical hypothyroidism occurred in 38% of cases. Gonadal damage was evident in the large majority of male patients but reversible in half of them, whereas permanent sterility was observed in females at least 35 years of age. No secondary leukemia has been so far detected. DISCUSSION: VEBEP followed by involved-nodal-field radiotherapy is an effective treatment for chemotherapy-naive Hodgkin's disease and is associated to acceptable rates of acute and intermediate-term toxicity. This intensive regimen, which does not routinely require the support of hematopoietic growth factors and can be delivered in an outpatient setting, warrants a prospective comparison in a randomized trial versus one of the more effective standard-combination regimens.

Adolescent↗

PubMedDate not supplied

[Microcalcifications in the diagnosis and follow-up after the primary chemotherapy of breast neoplasms].

Since 1998, at the National Cancer Institute (Milan, Italy), a study has been carried on relative to primary chemotherapy for locally advanced breast cancers (greater than 3 cm diameter). Aim of the study is to obtain tumor reduction and thus allow a conservative treatment to be performed. The measures of the two greatest diameters of the tumor by means of mammography, at diagnosis and after chemotherapy, are important parameters for treatment planning. Among the 213 patients who completed the whole diagnostic-therapeutic procedures by December 1990, the authors chose 94 cases (44%) presenting breast cancers with microcalcifications and reviewed the relative mammograms. The review was aimed at analyzing morphology, number and extent of the microcalcifications and at assessing their value as reliable parameters of cancer response to primary chemotherapy. In their experience, the authors found that increased visibility of the microcalcifications after chemotherapy is often due to a reduction in both edema and lesion opacity. On the contrary, fewer microcalcifications may be correlated with incisional diagnostic biopsies. In conclusion, if microcalcifications are a useful parameter for diagnosis, they alone are less important when evaluating response to primary chemotherapy, since they probably represent a permanent sign of the extent of the primary lesion. All follow-up mammograms of the patients who underwent conservative surgery were also reviewed: no residual microcalcifications or other suspicious abnormalities were observed.

Adult↗

PubMedDate not supplied

Flow cytometry to estimate circulating hematopoietic progenitors for autologous transplantation: comparative analysis of different CD34 monoclonal antibodies.

We report that the 2 fluorescein (FITC) conjugated CD34 monoclonal antibodies available to date, namely FITC-8G12 and FITC-QBEND10, exhibit different capabilities of detecting circulating hematopoietic progenitors (CHP) as cells expressing the CD34 antigen (CD34+) by direct immunofluorescence flow cytometry. Mean fluorescence intensity conferred by FITC-QBEND10 to CD34+ CHP is 2.8-4.3 times lower than that conferred by FITC-8G12. By indirect immunofluorescence, native unconjugated QBEND10 and 8G12 antibodies detect CD34+ CHP in a comparable manner, thus indicating that the decrease in QBEND10 affinity is due to FITC-conjugation. Utilization of FITC-QBEND10 instead of FICT-8G12 to estimate infrequent (usually less than or equal to 5%) CD34+ CHP for clinical decision-making in autologous transplantation of CHP exposes clinicians to the risk of either overestimating (false positive) or underestimating (false negative) these cells in peripheral blood. Recently published guidelines for large-scale collection of CHP for autologous transplantation in cancer patients were based on data obtained with FITC-8G12. The same guidelines cannot be considered valid if FITC-QBEND10 is employed. We recommend FITC-8G12 as the optimal reagent to date for standardizing results of autologous CHP transplantation in cancer therapy.

Antibodies, Monoclonal↗

PubMedDate not supplied

GM-CSF-exposed peripheral blood progenitors as sole source of stem cells for autologous transplantation in two patients with multiple myeloma.

Two patients (aged 52 and 44) received high-dose sequential chemotherapy followed by myeloablative therapy and autotransplantation as first line treatment of a stage III multiple myeloma with high plasmacell labelling index. Autograft was performed with peripheral blood cells collected after high-dose etoposide followed by rhGM-CSF continuous infusion. During this period very high numbers of circulating hemopoietic progenitors were detected in both patients. Prompt, complete and durable hematological recovery was observed after autograft with peripheral blood stem cells. Thus, we conclude that massively released progenitors after high-dose chemotherapy and rhGM-CSF include stem cells capable of marrow reconstitution.

Adult↗

PubMedDate not supplied

Heterogeneity of circulating hematopoietic progenitors in cancer patients treated with high-dose cyclophosphamide and recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF).

Antigen CD34+ cells represent 1-4% of adult bone marrow cells comprising virtually all hematopoietic colony-forming progenitors in-vitro and probably also stem cells capable of restoring hematopoiesis of lethally irradiated hosts. We report that sizable numbers of CD34+ cells transiently circulate in the peripheral blood (PB) of patients treated with high-dose (7 g/sqm) cyclophosphamide (HD-CTX) with or without recombinant human glycosylated granulocyte macrophage colony stimulating factor (rhGM-CSF). Evidence is presented demonstrating that CD34+ cells from PB possess qualitatively normal hematopoietic colony growth and high cloning efficiency similarly to marrow CD34+ cells. In addition, CD34+ cells from PB are shown to display heterogeneous flow cytometry characteristics and differentiation antigens analogous to those from bone marrow, i.e., CD34+/CD33-, CD34+/CD13-, CD34+/CD38-, CD34+/CD11b, CD34+/DRlow+ cells have light scatter properties of small lymphocytes while CD34+/CD33+, CD34+/CD13+, CD34+/CD38+, CD34+/CD11b+, CD34+/DRhigh+ cells have light scatter properties of blast-like cells. In HD-CTX treated patients, CD34+ cell circulation is 5-fold enhanced by rhGM-CSF 5.5 micrograms/kg/day by continuous iv infusion for 14 days. During the second-third week after HD-CTX, large-scale collection of PB leukocytes by 3-4 continuous-flow leukaphereses allows the yield of 2.19-2.73 x 10(9) or 0.45-0.56 x 10(9) CD34+ cells, depending on whether or not patients receive rhGM-CSF. The number of CD34+ cells retrieved from PB by leukaphereses exceeds the number that can be harvested by multiple bone marrow aspirations under general anesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

High-dose cyclophosphamide in patients with operable breast cancer: recombinant human GM-CSF ameliorates drug-induced leukopenia and thrombocytopenia.

Seventeen patients with breast cancer (nine patients with 10 ipsilateral metastatic axillary nodes, eight patients with inflammatory breast carcinoma) previously untreated with cytotoxic chemotherapy received high-dose cyclophosphamide, 7 g/sqm (HD-CTX) as initial step of a high-dose sequential chemotherapy program. Eleven patients received also intravenous recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF), 5.5 micrograms/kg per day for 7-14 days after HD-CTX. This growth factor significantly ameliorated leukopenia and thrombocytopenia induced by HD-CTX therapy thus allowing earlier delivery of subsequent courses of chemotherapy.

Adult↗