Mario V. Fiorentino

Intrapericardial instillation of platin in malignant pericardial effusion.

Six patients (four men and two women) affected by malignant pericardial effusion, as confirmed by cytologic examination, were treated with direct intrapericardial administration of cisplatin. Median age was 36.8 years (range, 18 to 56 years). After insertion of a radiopaque polyurethane catheter (Centracath Vygon, Laboratoires Pharmaceutiques, Vygon‐écouen, France), fluid was drained and cisplatin (10 mg in 20 ml of normal saline) was instilled over 5 minutes on 5 consecutive days (total cisplatin dose, 50 mg). At the end of the course, the catheter was withdrawn. Courses were repeated every 2 or 3 weeks in case of fluid reaccumulation. The median number of courses was two, with a range of one to three courses. Three patients achieved complete response and all three died of primary disease progression without evidence of pericardial recurrence or stricture. Mild nausea occurred in all patients. No hematologic and renal toxicity and local or infectious complications were observed.

Cisplatin, bleomycin and methotrexate in the treatment of advanced oesophageal cancer

From February 1981 to September 1982, 34 patients with metastatic or locally advanced (inoperable) epidermoid carcinoma of the oesophagus were treated with a combination of cisplatin, bleomycin and methotrexate. Thirty-one patients are now evaluable for response: 16 of 31 (52%) experienced some improvement, but only eight (26%) obtained major responses (one complete and seven partial). Responses were obtained rapidly within the first two courses. The median duration of responses was 5 months. The median survival from start of therapy was 8 months for responsive and 5 months for non-responsive patients. Gastrointestinal toxicity (cisplatin-related) and mild myelosuppression were the most prominent side-effects. This combination chemotherapy proved to be only of small efficacy in the long-term control of advanced oesophageal cancer. However, because the responses were obtained rapidly, it is conceivable that a similar regimen (with increased dosage of cisplatin) applied before surgery to patients with limited disease could obtain a reduction of the bulky tumour, with a possible increase of the resectability rate and destruction of micrometastases.

Treatment of multiple myeloma with M-2 protocol and without maintenance therapy

From September 1975 to December 1981, 63 consecutive untreated patients with multiple myeloma received the Lee M-2 protocol. We used the same drugs (melphalan, cyclophosphamide, vincristine, BCNU and prednisone) but employed the lowest suggested doses and recycled earlier, i.e. after 21-28 days. Thirty-five patients (62.5%) were in stage III, 16 (28.6%) in stage II and 5 (8.9%) in stage I. An objective response (reduction in paraprotein production rate greater than 50%) was obtained in 44 out of 56 cases (78%); 32 (57%) had a reduction greater than 75%. The median duration of response was 21.5 months. In responding patients the treatment was stopped after 1 yr and resumed only at relapse. Twenty-two out of 25 retreated patients are now evaluable. Eighteen of them (82%) responded again; in retreatment the degree of response was lower, but the duration of second response was only slightly lower than the first response (15.7 vs 21.5 months, NS). Of 7 patients receiving a third M-2 reinduction 4 responded again. The median survival for all the patients is 51 months. The high rate of second response to the M-2 regimen after an unmaintained remission brings into question the value of continuous therapy in responsive multiple myeloma.

FAM2 regimen in disseminated gastric cancer.

Forty-four previously untreated patients with advanced inoperable and/or disseminated gastric carcinoma were given an i.v. combination (FAM2) chemotherapy of 5-fluorouracil, 400 mg/m2 on days 1, 2 and 3, and 21, 22 and 23; adriamycin, 40 mg/m2 on days 2 and 22; and mitomycin C, 10 mg/m2 on day 1, with a recycle on day 42 (1 cycle = 41 days). Forty patients have completed 2 cycles and are evaluable (median number of cycles 5; range 3 to 8): 26 of these achieved a partial remission, with a response rate of 65 %; 4 (10 %) gained a stable situation for 3 to 6 months, and 10 (25 %) showed progression of disease. Median duration of partial remissions was 10 months, and median survival was 15 months for responders and 5 months for nonresponders. A fall in WBC (< 2500/μl) occurred in 7 % and of platelets (< 80,000/μl) in 4.5 %. Total alopecia occurred in 20 of 40 patients and nausea and or weakness were common findings. No drug-related infection, bleeding or death was observed. Patients with advanced gastric carcinoma can derive useful palliation from FAM2 chemotherapy.

Serum Lactate Dehydrogenase (LDH) as a Prognostic Index for Non-Hodgkin's Lymphoma"

According to pretreatment values of serum lactate dehydrogenase (LDH), 113 consecutive patients with non-Hodgkins lymphoma were divided into three levels: level 1 (within normal range) with LDH less than 250 U/l; level 2 (moderately increased) with LDH between 250 and 500 U/l; level 3 (highly increased) with LDH more than 500 U/l. LDH was elevated in 46 of 113 patients (41%). Normal values of LDH were associated with a better response to therapy and a longer survival, independent of histological type and clinical stage, with one exception; in stage IV patients conclusions could not be drawn concerning the response to therapy (complete remission occurred only in 8 of 44). Even though level 2 patients behaved slightly better than level 3 patients, no statistical difference has been observed between the two levels. Accordingly, serum LDH can be considered a useful predictor of response to therapy and of survival in non-Hodgkins lymphoma.

Secondary leukemia following treatment for Hodgkin's disease.

Aims and Background Patients treated for Hodgkins disease with chemotherapy or with the association of chemotherapy and radiotherapy have an increased risk of secondary leukemia. The aim of this study was to evaluate the leukemogenic risk due to these treatment modalities. Methods We performed a case-control study on a population of 1410 patients treated for Hodgkins disease from 1970 to 1990 in our Institute. Among these patients, we identified 25 cases of secondary leukemia and 3 cases of myelodysplasia, all occurring more than one year after the diagnosis of Hodgkins disease. Three cases occurred among the patients treated with radiotherapy alone. When we analyzed the risk in relation to the type of treatment (radiotherapy, chemotherapy, or both), the comparisons were relative to patients treated with radiotherapy alone. Results We found that chemotherapy alone is associated with a fivefold increased risk (odds ratio = 5.4) compared with radiotherapy alone. When both treatments are used, the risk is not further increased (odds ratio = 4.4). Patients receiving more than 6 courses of chemotherapy have an excess risk (relative risk = 2.5) compared with those treated with 6 courses or less. No increased risk was observed after splenectomy. Conclusions This study confirms an increased incidence of secondary leukemia occurring in patients treated for Hodgkins disease. The increased risk seems to be correlated with the number of courses of alkylating agent therapy, whereas it is unaffected by the addition of radiotherapy.

Peptichemio in pretreated patients with plasmacell neoplasms

Twenty-one patients with alkylator-resistant plasmacell neoplasms were treated with Peptichemio (PTC) at a dose of 40 mg/m2 for 3 days every 3 weeks or, in the case of persistent leukopenia and/or thrombocytopenia, at the single dose of 70 mg/m2 every 2-3 weeks according to haematological recovery. Seventeen patients, 10 with multiple myeloma and seven with extramedullary plasmacytoma (EMP), were fully evaluable. Six of 17 patients (35%) responded: three of seven EMP patients had a complete remission and 3 of 10 multiple myeloma patients had an objective response greater than 50%. The median duration of response was 8.5 months. An EMP patient obtained a complete response lasting for 16 months. The most frequent toxic effect were phlebosclerosis, occurring in all the patients, and myelosuppression, which was severe in only one case. PTC appears to be an active drug in patients with plasmacell neoplasms even if resistant to alkylating agents.

Lipid bound sialic acid in cancer patients.

Serum lipid-bound sialic acid (LSA) was measured with a recently described procedure in 108 healthy subjects and in 138 patients with a variety of solid tumors and hematologic malignancies. At the time of serum sampling, 128 patients had active disease and 10 patients had no evidence of disease. LSA was elevated in 104 of 128 (81.2%) patients with active disease, while carcinoembryonic antigen, analyzed in 74, was elevated only in 21 (28.4%) (P < 0.05). Sensitivity of the serum LSA test ranged from 66% for breast and gastrointestinal cancer to 92% for lung cancer. In patients with lung cancer, ovarian cancer or Hodgkins disease, LSA was correlated with the extent of disease and it also proved to be useful in following the course of disease. Our preliminary data indicate that this test can be used as a monitor of tumor burden.

Vindesine in the treatment of squamous cell carcinoma (WHO I), adenocarcinoma (WHO III), and large cell carcinoma (WHO IV) of the lung.

The antineoplastic activity of vindesine was evaluated in 57 patients with non-small-cell carcinoma of the lung. 53 patients were fully evaluable for response and toxicity. Twenty-seven patients had squamous cell carcinoma (WHO I), 14 had adenocarcinoma (WHO III), and 12 had large cell carcinoma (WHO IV). Forty percent of patients were previously treated. Vindesine was administered at a weekly i.v. dose of 3 mg/m2. Partial remissions were observed in 2 of 12 patients with large cell carcinoma and in 1 of 27 patients with squamous cell carcinoma. Among 14 patients with adenocarcinoma, 3 minor responses were observed. Drug-related toxic effects (mainly leukopenia with manageable and reversible neurotoxicity) required modification of dose in 41 % of patients: this finding and previous treatment may have adversely affected the response rate. It is concluded that vindesine as a single agent has some activity in large cell carcinoma. Activity in the other histologic types was minimal but not totally absent and deserves further evaluation, possibly in non-pretreated patients.

Tamoxifen treatment for advanced renal cell cancer.

Twelve patients with metastatic clear cell renal cancer received a course of tamoxifen. Three showed stable disease for a period from 2 to 12 months and 1 a mixed response for a short time. It does not appear that tamoxifen may be a useful agent in the treatment of metastatic renal cell carcinoma.