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From November 1981 to February 1983, 64 patients with advanced head and neck squamous carcinoma were randomly treated with either high-dose (120 mg/m2) or low-dose (60 mg/m2) cisplatin. Of the 62 eligible patients, 59 were evaluable: the response rate observed in patients receiving high-dose and low-dose cisplatin was 16.1% and 17.8%, respectively. Survival was superimposable in the two treatment arms. No evidence of dose dependency of cisplatin activity in advanced head and neck squamous carcinoma was noted in this randomized trial.

The pathologic and clinical findings of 50 patients aged 65 or older (median, 71.5 years) with non-Hodgkin's lymphomas (NHL) are reported. These patients formed 27% of all cases of NHL seen in a single institution over a 7-year period. Forty patients presented with nodal and 10 with extranodal NHL. According to the Ann Arbor system, 20 were clinical and/or pathologic Stages I and II, and 30 were Stages III and IV; of the 10 patients presenting with extranodal NHL, 8 were Stages I and II. Histologically, 84% of the cases were of the intermediate and high-grade groups according to the Working Formulation; diffuse histiocytic was the most frequent histotype (34%) according to the Rappaport classification. The pattern was diffuse in 94% of the cases. Five patients received no treatment; treatments were conservative (monochemotherapy and/or local radiotherapy) in 19 patients and aggressive (polychemotherapy and/or extended-field radiotherapy) in 26. Four patients of the latter group died of toxicity; 22 patients died of lymphoma and 13 of other causes; the other 11 (22%) patients are still alive. The overall median survival was 2.2 years. A significantly better survival was observed in patients with Stages I and II (P less than 0.025) and in those with intermediate grade (P less than 0.05) when compared with patients having Stages III and IV and high-grade histology, respectively. Apparently, no significant difference both in response and survival was found between the groups of patients which arbitrarily underwent conservative or aggressive treatments on the basis of their general conditions. Randomized clinical trials should be designed in order to draw more significant conclusions on the correct management of elderly patients with NHL.

Forty-six evaluable postmenopausal patients with locally advanced, inoperable T3-T4 breast carcinoma were treated with tamoxifen 10-20 mg twice daily for a period at least 6 weeks. Eight patients (17 %) had an objective response at the primary tumor site after 6 weeks of treatment. Improvement of response with a further single tamoxifen therapy was observed in 7 patients, resulting in an overall objective response in 14 of 46 (30 %). Median duration of response was 8 months (range 2-24). No response was obtained in the 5 patients with inflammatory signs. Toxicity of treatment was minimal. Median survival was 10 months (responders 17.5, non-responders 9). Tamoxifen seems to be a safe and effective treatment for locally advanced breast cancer without inflammatory signs in postmenopausal women.

Carcinoembryonic antigen (CEA) assays (2536) were performed in 380 disease-free breast cancer patients after radical mastectomy. In the 334 evaluable patients with 3 or more determinations, the overall relapse rate after a median follow-up of 29 months was 11 %. Of 203 patients with normal CEA values, 19 (9.3 %) relapsed. In the 50 patients with the highest CEA value greater than 20 ng/ml, the relapse rate was 26 %; in the 12 patients with gradually increasing CEA elevations it was 50 %. However, CEA was unable to predict recurrence in N- patients. Premastectomy N+ was significantly associated with greater than 20 ng/ml or gradually increasing CEA values, suggesting the lack of an independent prognostic value of CEA in our patient population.

A group of 38 patients with a median age of 70 years and chronic lymphocytic leukemia (CLL) were treated using a cobalt 60 U or a 6-MeV linear accelerator. A direct field or two opposite fields covered the palpable spleen area in most patients. 100 cGy were administered weekly for a total dose of 10 Gy, given over 10 weeks. The stage arrangement (according to Rai) for the 32 evaluable patients was as follows: Stage I: 11 patients, Stage II: nine patients, Stage III: three patients, and Stage IV: nine patients. Patients in Stages I and II were treated when symptomatic. Twenty-five patients (78%) achieved hematologic response (HR), defined as normalization of the differential leukocyte count, of the total blood cell count, and of bone marrow infiltration. However, no complete response according to the standard criteria of response has been obtained. The median response time of HR was 7 months (range, 1.5 months to greater than 120 months). The overall median survival time from the start of splenic irradiation (SI) was 40 months. More than 50% splenomegaly reduction was obtained in 63% of patients, whereas no benefit was verified in the lymphadenopathy. The incidence of second tumor was 29%. Fourteenmore » patients benefited from a further 21 SI cycles. SI does not result in a complete remission and therefore cannot modify the course of CLL. This treatment is most advisable for elderly patients with predominant bone marrow lymphocytosis, for patients with previous extensive chemotherapy or radiotherapy, and for patients with poor marrow reserve. Moreover, because of the absence of toxicity subsequent treatment is not compromised.« less

Twenty-three consecutive patients with cutaneous T-cell lymphomas were submitted to staging procedures including lymphangiography, bone marrow biopsy and aspiration, peripheral blood morphological examination, peritoneoscopy with liver and spleen biopsy, and in selected patients lymph node biopsies. Extracutaneous disease (lymph nodes, bone marrow, liver and spleen) was detected in 12 patients. Bone marrow was involved in 25 per cent of the patients at presentation (all patients had lymph node involvement) and in two of nine patients with advanced disease during the follow-up. Peripheral blood was involved in 65 per cent of the patients at presentation (ten patients with advanced disease) and in six of nine patients with advanced disease during the follow-up. In 16 patients with advanced disease (T3-T4 and/or extracutaneous disease), CVP was given with a 50 per cent objective response rate and four complete remissions of 47+, 12+, 19 and 19 months duration. Median survival of patients with advanced disease was 4 years.

From September 1979 to December 1983, a phase II trial with teniposide (VM-26) in multiple myeloma (MM) was conducted at our institution. Of the 30 patients entered, 25 were evaluable for response, 12 previously treated with M-2 protocol and 13 previously untreated elderly (greater than or equal to 70 years) patients. A median of nine cycles (range 1-21) of VM-26 was administered. Seven responses (28%) according to Myeloma Task Force criteria were observed with a median duration of 4 months (range 2-12+). Four responses (33%) were observed in the 12 previously treated patients. Overall toxicity was mild. VM-26 seems an active drug in MM, without significant toxicity even in elderly patients.

Between July 1981 and December 1983, 63 patients, with brain metastases were treated with an accelerated split course regimen; irradiation was given to the whole brain in 3 daily fractions of 160 cGy each (with 4h interval between the fractions), for 5 days a week. The cycle was repeated after 2 weeks to a total dose of 4800 cGy. Male-female ratio was 3:1 (48 males and 15 females). Median age was 58 years (range 24 to 75). The most frequent site of primary tumor was lung (squamous cell carcinoma in 33 patients and oat cell carcinoma in 8 patients), breast in 6 patients, melanoma in 3 patients, other sites in 8 patients and unknown cancer in 5 patients. Thirty-five patients had multiple brain metastases localizations. In 33 patients (52.3%), metastases were present in other sites outside the central nervous system. Two patients failed to complete the scheduled treatment: one because of early death and the other by refusal of therapy during treatment. We obtained complete remission (CR) in 4 patients and partial remission (PR) in 24 patients. The median survival time was 21 weeks. The overall response rate was 42.5%. Toxicity was not considerable. The treatment results were not influenced by the site of primary tumor or by disease spreading; only the neurologic status before radiotherapy and the response to treatment influenced survival. The results we obtained are similar to those reported by other studies; however, with the accelerated split course regimen the treatment time was reduced and a shorter period of hospitalization was required.

From December 1981 to November 1982, a consecutive series of 37 patients with advanced non-oat cell bronchogenic carcinoma were treated with cis-platinum and etoposide in doses of 20 mg/m2 and 75 mg/m2, respectively, for 5 consecutive days every 3 weeks. Among the 33 evaluable patients, one complete response, 11 partial responses, five minor responses, seven unchanged states, and nine cases of progression were noted. Median duration of response was 30+ weeks. Toxicity was significant, but no treatment-related deaths were encountered. Combined cis-platinum and etoposide can provide significant palliation in approximately one-third of patients with the doses and schedule used.

Twenty-two consecutive patients with recurrent malignant brain tumors after radiation therapy and systemic combination chemotherapy with BCNU and vincristine, four of whom were not evaluable due to early death, were treated with etoposide (VP-16-213) (50-100 mg/m2 for five days every three weeks). Response, defined as improvement in both clinical examination and computed tomography scan in absence of glucocorticoids dosage increase, was observed in three (17%) of 18 evaluable patients, lasting greater than 21, seven, and two months, respectively. Six additional patients had stable disease for greater than 10, seven, four, four, three, and two months: all of them had improvement of clinical symptoms but no variation in their scans. Overall median survival from the start of VP-16-213 was 4.5 months (range, 1-23 + months), whereas patients with response or stable disease had a median survival of eight months. Overall, treatment was well tolerated. In 10 patients concomitant plasma and cerebrospinal fluid samples were evaluated with a high-performance liquid chromatographic method for drug assay. The concentration of VP-16-213 in cerebrospinal fluid was less than 1% that found in plasma, even in the two patients with response. The activity of etoposide in patients with malignant, lomustine-vincristine-resistant brain tumors suggests an interesting potential use for this drug.

We tested VP 16-213 in 16 patients with advanced head and neck cancer after conventional treatments. VP 16-213 was administered orally at the dosage of 100 mg/mq for 5 consecutive days every 3 weeks. No patient achieved an objective response. Toxicity was mild. VP 16-213 given at this dose and schedule revealed no activity in pretreated patients with head and neck cancer.

From May 1980 to November 1981, 51 consecutive patients with locally advanced, recurrent or metastatic head and neck squamous carcinoma were treated with 2 successive outpatient chemotherapeutic regimens including adriamycin, cyclophosphamide, vincristine, bleomycin, methotrexate and 5-fluorouracil with or without mitomycin-C. A 34% objective response rate was obtained with acceptable toxicity and good patient compliance. The presence of mitomycin-C did not influence response rate. Median survival was 9 months.

From October 1978 to June 1981, 35 consecutive patients with grade III-IV malignant glioma were treated with a concentrated course of radiotherapy (two cycles of 17 Gy in two sessions over a 3-day period) with a cobalt unit, followed by chemotherapy with vincristine and BCNU. In the 30 evaluable patients, no complete remission, seven partial remissions, 23 stable disease, and no progression were encountered. Median duration of response was 6 months (range 4-11+). Median survival time was 9 months (range 7-19); radically resected patients survived longer than those with inoperable tumor. Toxicity of treatment was acceptable; however, two patients with brain stem tumors had acute neurologic toxicity following the first radiotherapy session.

Experience with a multiple fractions per day radiation therapy program for inoperable esophageal cancer is reported. The treatment program consisted of 3 daily fractions of 1.6 Gy, with a 4 hr interval between fractions, for 5 consecutive days (24 Gy). After a rest period of 2 weeks, a second course of radiation was given with the same dose and fractionation for a total dose of 48 Gy in an overall treatment time of 4 weeks. Thirty-four patients were treated between February 1981 and July 1983. Acute reactions consisted of mild esophagitis noted in 30% of patients. No treatment related complications were reported. Median survival was 7 months and the 2- and 5-year survival rates were 12 and 9%, respectively. Tumor size and Karnofsky performance status were found to be the most important prognostic indicators for prolonged survival. Prompt palliation of symptoms was noted. Thirty-three per cent of patients had complete resolution and 41% had partial improvement of symptoms after completion of treatment. Four patients (12%) obtained complete tumor regression with negative biopsy at endoscopic examination and 2 of them are free of disease at 58 and 64 months. A partial response was reported in 12 patients (35%) for a median duration of 5 months (3-26). Treatment with multiple fractions per day was feasible in patients with esophageal cancer and could be preferred to more conventional fractionations for promptness of palliation and the shorter treatment time. The expected therapeutic gain is discussed.

From April 1981 to December 1981, 34 consecutive patients with advanced gastrointestinal cancer were treated with chlorozotocin at the dosage of 40 mg/m2 daily for 5 consecutive days (30 mg/m2 in patients pretreated with chemotherapy) every 6 weeks. In the 30 patients evaluable for response, a 3.3% objective response rate was encountered. Toxicity was not significant and consisted mainly in reversible myelosuppression. Median survival was 3 months. At the dosage and schedule used, chlorozotocin does not seem to be an effective agent in the treatment of advanced gastrointestinal cancer.

From January 1975 to December 1979, 14 consecutive patients with advanced (stage III-IV) diffuse lymphocytic, poorly differentiated lymphoma (DLPD) were treated with adriamycin, bleomycin, vinblastine and DTIC (ABVD). Either maintenance combination chemotherapy with CVP or radiotherapy over bulky disease was added in the cases with complete response (CR). Fifty per cent of the patients achieved CR and 80% achieved objective responses. Among CRs, 100% were alive at 2 years, 70% of them without evidence of disease. Overall, 75% of the patients were alive at 2 years, 30% without evidence of disease. Toxicity was acceptable and no drug-related deaths occurred. ABVD is not the ideal combination for DLPD, but it should be taken into consideration in patients with advanced DLPD in which first line combination chemotherapy regimens are not successful.

From January 1975 to March 1981, 97 consecutive patients with brain metastases from various tumors were treated with cobalt-radiotherapy. Two successive treatment schedules were employed: the first 52 patients were treated according to a conventional schedule (30 or 40 Gy in 15 or 20 treatments over a 3 or 4 week period), while in the successive 45 patients a concentrated schedule was employed (2 series of 17 Gy in 2 sessions over a 3 day period, separated by an interval of 3 weeks). In the 87 evaluable patients, no significant difference was noted regarding the efficacy of radiotherapeutic treatment (25/47 and 20/40 partial remissions, respectively, with median survival of 4 and 3 months, respectively). Acute toxicity was more relevant with concentrated irradiation (approximately 20% of cases).