Adriano Fornasiero

Chemotherapy for invasive thymoma: A 13-year experience

From 1977 to 1990, 37 patients with Stage III or IV invasive thymoma (20 men and 17 women; median age, 40 years of age) were referred for chemotherapy to the Padova Medical Oncology Department. All patients initially received the same regimen (50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously (IV) on day 1, 0.6 mg/m2 of vincristine IV on day 3, and 700 mg/m2 of cyclophosphamide IV on day 4 [ADOC]), recycling at monthly intervals. No life‐threatening side effects were noted. The overall clinical response rate (complete response plus partial response) was 91.8%, with 43% complete remissions. Median duration of response and survival were 12 months (range, 2 to 96+ months) and 15 months (range, 5 to 96+ months), respectively. Seven of the 16 complete remissions were pathologically confirmed at subsequent thoracotomy. Other chemotherapy combinations and radiation therapy have been applied as second‐line treatment, achieving only minimal responses. In the opinion of the authors, such chemotherapy deserves evaluation for adjuvant and neo‐adjuvant treatment of invasive (and/or inoperable) thymoma due to the high complete response rate and overall response rate.

Treatment of metastatic carcinoids and other neuroendocrine tumors with recombinant interferon‐alpha‐2a: A study by the Italian trials in Medical Oncology Group

Background. Using a wide range of interferon (IFN) doses and schedules, a number of authors have found them to be active against neuroendocrine tumors.

PREOPERATIVE COMBINED RADIOTHERAPY AND CHEMOTHERAPY FOR MIDDLE AND LOWER RECTAL CANCER: PRELIMINARY RESULTS

Background: Adjuvant treatment for rectal cancer is still controversial. This study reports on overall survival and disease-free survival, toxicity, downstaging, and surgical morbidity in rectal cancer patients who received combined chemoradiation therapy followed by curative surgery.Methods: Between 1993 and 1998, 51 patients (31 males and 20 females; median age, 60 years; range, 33–73 years) underwent chemoradiation therapy followed by radical surgery for middle and lower rectal adenocarcinoma. Criteria for giving preoperative radiotherapy (total 45 Gy in 25 fractions of 1.8 Gy/day for 5 weeks) and chemotherapy (5-fluorouracil 350 mg/m2/day and leucovorin 10 mg/m2/day, bolus on days 1–5 and 29–33) were an age younger than 75 years; an Eastern Cooperative Oncology Group performance status score of 0 to 2; and clinical preoperative stage II–III. Forty-three low anterior and eight abdominoperineal resections were performed. Median follow-up time was 29 (range, 3–63) months.Results: Although grade 3 to 4 toxicity occurred in 14 cases (27.4%), all patients completed the planned adjuvant therapy. At pathology, a complete response was found in eight (15.7%) cases. Of the remaining 43 cases, 22 were stage I, 12 were stage II, and 9 were stage III. Five-year actuarial disease-free survival and overall survival rates were 86.4% and 85.5%, respectively. Whereas no local recurrences were found, 4 patients had distant metastases. Three patients died (1 of cancerrelated causes), 45 are alive and disease free, and 3 are alive with disease.Conclusions: The combined preoperative chemoradiation approach used by us seems to improve the disease-free survival and overall survival of selected patients with rectal cancer. However, a longer follow-up time is required to confirm these preliminary results.

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.

Prognostic factors in resectable gastric cancer: Results of EORTC study no. 40813 on FAM adjuvant chemotherapy

AbstractBackground: The high incidence of locoregional recurrences and distant metastases after curative surgery for gastric cancer calls for improved locoregional control and systemic adjuvant treatment. Methods: In a randomized clinical trial on adjuvant FAM2 chemotherapy, quality of surgery was evaluated by comparing surgical and pathology data. Univariate and multivariate analysis was made to evaluate the effect of prognostic factors on survival and time of recurrence in relation to patients, tumor, and therapy. Results: Of 314 patients randomized from 28 European institutions, 159 comprised the control and 155 the FAM2 group. After a median follow-up of 80 months, no statistically significant difference was found between survivals. However, for recurrence time, treated patients had a significant advantage over controls (p=0.02). At univariate analysis, statistically significant differences in survival and time to progression emerged for T, N, disease stage, and “adequacy” of surgery. The multivariate analysis retained preoperative Hb level, T, N, and “adequacy” of surgery for time of survival; and T, N, “adequacy” of surgery and adjuvant chemotherapy for recurrence time. Conclusions: Disease stage is the most important prognostic factor. “Adequate” surgery has an important effect. Adjuvant FAM2 delayed time of recurrence, but did not influence overall survival.

Alpha-2 interferon and 5-fluorouracil in advanced colorectal cancer.

A total of 21 untreated patients (5 males, 16 females; median age, 55 years; range, 28-72) with advanced measurable colorectal carcinoma were treated with an association of 5-fluoro-uracil (1000 mg/weekly) and alpha-2 interferon (three times a week s.c.: 6×106 U in the 1st month, 9×106 U in the 2nd month, 12×106 U in the 3rd month and then 18×106 U) until maximum response or progression of disease. Sites of disease involved liver in 10 patients, lung in 6, supraclavicular lymph nodes in 3, skin in 1, abdomen in 4, and vagina in 1 patient. Nine responses (42.8%) were documented (4 complete and 5 partial) with metastases confined to the liver, lung, nodes and skin. Median duration of response was 11 months (range, 4-17+) and median survival was 10 months (range, 2-17+). Side effects (fever, flu-like syndrome and leukopenia) required a dose reduction of 5-fluorouracil In 8 patients and interferon in 2 patients.

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.

Combination goserelin and tamoxifen therapy in premenopausal advanced breast cancer: a multicentre study by the ITMO group

It has been suggested that tamoxifen may improve the efficacy of medical castration with luteinising hormone-releasing hormone analogues, but very few data have so far been published concerning the clinical and endocrinological activity of this therapeutic modality. In this phase II multicentre trial conducted by the Italian Trials in Medical Oncology group (ITMO), 64 premenopausal patients with hormone receptor-positive or unknown breast cancer were treated with monthly s.c. injections of goserelin 3.6 mg, in association with a tamoxifen daily dose of 20 mg, as first-line therapy for their advanced disease. All of the patients were evaluable for efficacy and there was an overall response rate of 41% (95% confidence interval 28-52%), with 7 of the 26 responders achieving complete remission. The median time to response was 4 months (range 2-17), and the median response duration was 13 months (range 6-37 +). Better responses were observed in soft tissues (51%); the response in visceral and bone metastases was respectively 19% and 37%. Serum concentrations of gonadotrophins and oestradiol were significantly decreased by the treatment, oestrogen levels being constantly suppressed to within the range observed in post-menopausal women. No significant change was detected in serum testosterone levels. In our experience, although it was not associated with any increased clinical efficacy, the concurrent use of goserelin and tamoxifen proved to be a feasible approach in the management of premenopausal advanced breast cancer.

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.

Adjuvant treatment for gastric cancer.

In spite of progress made in surgical techniques and intensive care, only a slight improvement in the therapeutic control of gastric carcinoma has been achieved in the last 20 years. In this paper we present a review of controlled clinical trials on adjuvant chemotherapy and chemo-immunotherapy for gastric cancer and this topic is discussed in the light of our experience and that of the Gastrointestinal Group of the European Organization for Research and Treatment of Cancer. The results of adjuvant therapy are less satisfactory in Western countries than in Japan. The efficacy of the 5-fluorouracil + adriamycin + mitomycin C regimen in advanced gastric cancer has not been confirmed in an adjuvant setting. The therapeutic benefit reported in Japanese studies may be due to a chemotherapy started intraoperatively or during the immediate postoperative period and should also be considered in the light of a standardized surgical treatment. The new therapeutic trends, using recent chemotherapeutic associations tested in Phase I and II clinical trials or combining traditional chemotherapy with different types of immunostimulators, are discussed. Only when large-scale clinical studies have been made will it be possible to confirm their therapeutic efficacy.