Extended-field radiotherapy in favorable stage IA-IIA Hodgkin's disease (prognostic role of stage).

PURPOSE: The study was undertaken to evaluate the long-term results in a favorable subset of patients with pathological Stage IA-IIA treated with irradiation alone. METHODS AND MATERIALS: One hundred and forty-seven adults with laparotomy- Staged IA-IIA "favorable" Hodgkin's disease were treated with primary subtotal nodal irradiation. Patients with infradiaphragmatic presentation were irradiated through paraortic and inguino-iliac node chains (inverted Y field) followed by prophylactic mediastinal and supraclavicular fields. RESULTS: Actuarial overall survival (OS) at 7 years (median follow-up 77 months) was: 93% for the whole series, 94% for Stage I, and 92% for Stage II. The freedom from first progression (FFP) (80% for the whole series) showed a statistically significant difference (p = 0.008) between Stage I (88%) and Stage II (71%). By univariate analysis, stage alone had an independent prognostic significance for OS and FFP. Of the 29 relapsed patients, 8 were previously classified as Stage I and 21 as Stage II; 16 of 29 (55%) of the relapses occurred in the pelvis and 9 in extranodal sites. After salvage treatment with chemotherapy all patients achieved a second complete remission. Seven second malignancies (two acute nonlymphocytic leukemias, one preleukemic syndrome, and four solid tumors) have been detected so far. Hypothyroidism was observed in 16% of patients and a reversible pulmonary restrictive syndrome in 14% of cases, respectively. CONCLUSIONS: Within 7 years from radiation therapy, about one-quarter of the patients with Stage II disease will experience a relapse and need intensive salvage chemotherapy. This is not invariably successful and safe, for it may be complicated by either acute or potentially fatal long-term adverse effects, such as second malignancies and cardiac or pulmonary sequelae, in about 5% of patients. The high frequency of relapse in Stage IIA patients suggests a combined modality approach with relatively short-term chemotherapy not including alkylating agents.

Alternating versus hybrid MOPP-ABVD in Hodgkin's disease: the Milan experience.

The long-term therapeutic results achieved in a previous randomized study on stage IV Hodgkin's disease confirm the superiority of MOPP monthly alternated with ABVD compared to MOPP alone. To more closely meet the requirements of the Goldie and Coldman hypothesis, we activated a randomized study testing MOPP-ABVD through two different sequences in July 1982. One arm consisted of monthly alternating one cycle of MOPP and one cycle of ABVD; in the other arm, one half cycle of MOPP was alternated with one half cycle of ABVD within a one-month period (hybrid regimen). Each regimen was given to complete remission plus two consolidation cycles (minimum six cycles). After maximal tumor shrinkage, moderate doses of radiotherapy (25-30 Gy) were delivered to the lymphoid region(s) if bulky at the start of chemotherapy. A total of 300 patients with stage IB, IIA bulky, IIB, III (A + B) and IV Hodgkin's disease previously untreated with chemotherapy or failing after extensive irradiation were evaluated. At a median follow-up of five years, alternating and hybrid regimens yielded superimposable treatment outcomes: complete remission 89 versus 88%, freedom from first progression 65 versus 70%; relapse-free survival 72 versus 78%, overall survival 81 versus 80%, respectively. Tumor cell burden expressed as number of involved nodal sites and presence of pulmonary hilus involvement were the prognostic variables able to significantly influence treatment outcome. Conversely, stage, constitutional symptoms, and histology had no impact on the five-year results.(ABSTRACT TRUNCATED AT 250 WORDS)

Testicular dysfunction in Hodgkin's disease before and after treatment.

Over a 7-year period, semen analysis was performed in 92 male patients with Hodgkin's disease prior to therapy. In 67% of patients semen revealed a decreased chance for fertility (i.e. oligozoospermia, asthenozoospermia and/or teratozoospermia). The mean basal levels of follicle-stimulating hormone (FSH), luteinising hormone, testosterone and prolactin were in the normal range. In 77 patients in complete remission after alternating MOPP/ABVD (mechlorethamine, vincristine, procarbazine, prednisone; doxorubicin, bleomycin, vinblastine, dacarbazine), testicular function was assessed. 87% of patients were azoospermic, 9% had semen abnormalities and only 4% were normospermic. Recovery of spermatogenesis was documented in only 17 of 42 (40%) reassessed patients after a median time of 27 months and was generally not affected by pretreatment sperm quality. After chemotherapy, the mean value of FSH [20.45 (S.E. 1.7) mUI/ml] was significantly superior compared with that of the mean pretreatment values. No difference was documented in the mean testosterone and prolactin values tested before and after treatment. Our findings indicate that, of patients with Hodgkin's disease, about half are affected by hypogonadism before starting chemotherapy. By utilising alternating MOPP/ABVD, persistent testicular dysfunction was documented in half of the patients.

Phase II study of interferon alpha-2a and dacarbazine in advanced melanoma.

Based on the report of some activity of combination therapy with dacarbazine (DTIC) and interferon alpha-2a (rIFN alpha-2a) in disseminated melanoma, we conducted a phase II study to determine the feasibility and efficacy in a large series of patients. DTIC was administered in 79 patients at the dose of 800 mg/m2 every 3 weeks and rIFN alpha-2a was given daily at the dose of 9 X 10(6) IU for the first 10 weeks and three times a week thereafter. Among the 75 evaluable patients, 25% achieved an objective response, with 8% complete and 17% partial remissions. The regression occurred within a mean time of 1.9 +/- 1.03 months from starting therapy and the mean duration of response was 8.2 +/- 4.2 months. The major side effects were vomiting, anorexia, fever, fatigue, and myalgia. There was one death related to sepsis after myelosuppression. In the other patients bone marrow and liver toxicities were not remarkable. Our data reveal that a combination regimen of rIFN alpha-2a with a cytotoxic agent has some therapeutic activity in the management of advanced malignant melanoma.

Preliminary studies on melatonin in the treatment of myelodysplastic syndromes following cancer chemotherapy.

Experimental studies have suggested that the pineal hormone melatonin, in addition to its documented antineoplastic action, plays a role in the physiological regulation of blood cell proliferation. Based on these data, we evaluated the clinical effects of melatonin therapy in patients with myelodysplastic syndrome (MDS) secondary to cancer chemotherapy for primary neoplasms. The study was carried out on six patients, and melatonin was given orally at a dose of 20 mg/daily, following a schedule prepared to reproduce the circadian rhythm of the pineal hormone. A transient improvement in platelet and neutrophil count was achieved in two of five patients with thrombocytopenia and in two of four patients with neutropenia before therapy, respectively, while no effect was seen on hemoglobin concentration. Mean survival time was 12.5 months, and a long survival, greater than 30 months, was achieved in two of six patients. These preliminary results seem to suggest that melatonin may have a role in the treatment of MDS induced by previous cancer chemotherapy.

Salvage chemotherapy in Hodgkin's disease. Results in patients relapsing more than twelve months after first complete remission.

Forty-nine patients with Hodgkin's disease who relapsed after a first complete remission of more than 12 months following primary chemotherapy were treated with salvage therapy regimens. A total of 41 patients (84%) achieved complete remission. In particular, complete response was documented in 17 of 19 patients re-treated with the same initial drug combination. The five-year freedom from progression, relapse-free and overall survivals were 51%, 57% and 65%, respectively. In our experience, consolidation radiotherapy following drug-induced remission failed to improve the five-year relapse-free survival. Present findings indicate that about half of patients relapsing after a disease-free interval exceeding 12 months can remain alive and disease-free 5 years after starting salvage chemotherapy.

Timing of surgery and the role of cytoreductive chemotherapy in patients with advanced ovarian carcinoma.

We retrospectively selected 27 consecutive patients with advanced ovarian carcinoma (15 stage III, 11 stage IV and 1 relapse) who had an unresectable intraabdominal tumor at presentation and prospectively evaluated the overall treatment outcome. Patients were initially treated with chemotherapy consisting of cisplatin-containing regimens in 20 cases, adriamycin and cyclophosphamide in 5, and melphalan in 2. Treatment was continued until maximal tumor response or progression. Following a median of 6 cycles of chemotherapy, all patients underwent debulking surgery. Six women were without evidence of disease and 13 had minimal residual disease after surgery, for an overall 70% rate of optimal debulking. Patients with evidence of disease at laparotomy were treated with 5 additional cycles of chemotherapy, and response was then assessed at laparotomy except for patients with progressive disease. Nine (33%) patients were pathologic complete responders at the end of the entire treatment program. Overall median survival time was 26 months, with a median relapse-free survival of 33 months. Tumor responses were not associated with any particular chemotherapy regimen. The results achieved in this series of patients together with the data from the literature suggests that use of a cytoreductive chemotherapy of short duration has the potential of increasing the rate of optimal debulking surgery. Furthermore, it may contribute to a better disease control in women with bulky ovarian carcinoma compared to the present strategy, which consists of surgery followed by chemotherapy.

Morphologic, immunologic, and cytogenetic characteristics of secondary acute unclassifiable leukemia in Hodgkin's disease.

Blast cells from five cases of secondary unclassifiable leukemia following therapy for Hodgkin's disease were studied by cytochemical, immunological and cytogenetic analyses. Cytochemical and immunological reactivity were in accordance with poorly differentiated, myeloid blasts. The four cases in which karyotype analysis was performed showed specific chromosomal abnormalities. No evidence of multiple lineage involvement was found. Problems in classifying these cases of secondary ANLL were due to the high grade of undifferentiation of the blast cells. Their low cytochemical reactivity with markers of myeloid differentiation was similar to what may be observed in patients with acute undifferentiated leukemia or with chronic myeloid leukemia in blast crisis.

Phase II study with ifosfamide in advanced malignant melanoma.

Ifosfamide was tested in a phase II study in 12 evaluable patients with advanced malignant melanoma. The drug was administered at the dose of 3 g/m2 on days one and two every 3-weeks. Seven patients were not previously treated and 5 received only minimal prior chemotherapy. Visceral involvement was present in 9 patients, and the remaining 3 had only soft tissue lesions. No patient showed objective tumor response. Mild vomiting was observed in 75% of patients; alopecia occurred in all of them. No other major side effects were observed, in particular, myelotoxicity and urotoxicity. Lack of response advised us to discontinue patient accrual. Our data do not support a therapeutic role of ifosfamide at the given dose schedule in the treatment of metastatic malignant melanoma.