Publications by Year: 1999

1999
Papadimitris C, Dimopoulos MA, Kostis E, Papadimitriou C, Anagnostopoulos A, Alexopoulos G, Papamichael C, Gika D, Mitsibounas D, Stamatelopoulos S. Outpatient treatment of neutropenic fever with oval antibiotics and granulocyte colony-stimulating factor. Oncology [Internet]. 1999;57(2):127 - 130. WebsiteAbstract
In recent years, several cancer patients who developed neutropenic fever were effectively treated on an outpatient basis with either intravenous or oral antibiotics. This approach is associated with reduced cost and improved patient convenience. However, the appropriate antibiotic regimen and the role of growth factors have not been established yet. In order to address these issues we performed a nonrandomized phase II study to assess the feasibility and efficacy of an oral antibiotic regimen in combination with granulocyte colony-stimulating factor (G-CSF) for the outpatient treatment of cancer patients with low-risk neutropenic fever. In 50 patients with solid tumors or lymphoma, 60 episodes of neutropenic fever were treated with the combination of oral ofloxacin 400 mg twice a day, oral amoxicillin 1 g 3 times a day and G-CSF 5 μg/kg/day subcutaneously. Patients receiving G-CSF prophylaxis were eligible for our study. Oral antibiotics were administered for at least 5 days and G-CSF was continued until resolution of neutropenia. Our patients were ambulatory, hemodynamically stable, and without significant comorbidity. Our combination was successful in 57 episodes (95%) with a median time for fever resolution of 3 days (range: 1-5 days). There was no significant toxicity associated with the antibiotic regimen with the exception of one case of reversible renal impairment. The role of G-CSF in the success of our antibiotic treatment is highly questionable since one half of our patients developed fever while on G-CSF prophylaxis. The combination of oral ofloxacin and amoxicillin with G-CSF is highly effective for the outpatient treatment of cancer patients who develop uncomplicated febrile neutropenia. The relative contribution of G-CSF needs clarification with a prospective randomized study.
Mandrekas DP, Dimopoulos AM, Moulopoulou D, Papamichalis G, Gougoulakis AG. Distant cutaneous metastasis from carcinoma of the uterus. A case report. European Journal of Gynaecological Oncology [Internet]. 1999;20(3):212 - 213. WebsiteAbstract
Cutaneous metastasis from intraabdominal carcinoma is relatively rare. When it is present it is usually located in the skin overlying the neoplasm. Carcinoma of the uterus metastatic to the skin accounts for 9% of all cutaneous metastases. Distant metastasis is extremely rare. Such a metastasis to the skin of the big toe of the lower limb is presented.
Moulopoulos LA, Dimopoulos MA, Vourtsi A, Gouliamos A, Vlahos L. Bone lesions with soft-tissue mass: Magnetic resonance imaging diagnosis of lymphomatous involvement of the bone marrow versus multiple myeloma and bone metastases. Leukemia and Lymphoma [Internet]. 1999;34(1-2):179 - 184. WebsiteAbstract
Bone metastases from solid primary tumors, as well as multiple myeloma and secondary lymphoma may all present with bone lesions and associated soft-tissue masses on magnetic resonance images of the spine. In bone metastases and myeloma, the cortex of the affected bone is usually destroyed and a bulging contour is observed at the site of extraosseous spread. In cases of lymphomatous involvement of the bone marrow, however, we have observed that spread to the extraosseous soft-tissues occurs without alteration of the shape or contour of the affected bone. In order to assess whether this pattern of spread is indeed suggestive or even diagnostic of lymphoma of the bone marrow, we reviewed spinal bone marrow MR images of 66 patients, with bone metastases from solid primary tumors (33 patients), multiple myeloma (20 patients) and stage IV lymphoma with bone marrow involvement (13 patients), who had bone lesions and contiguous soft-tissue masses. If tumor was present on either side of the bony cortex but the contour of the affected bone was preserved, a 'wrap-around' sign was diagnosed. A 'wrap-around' sign was found in 12 of the 13 patients with lymphoma but in none of the patients with metastases or myeloma. On MR images of the bone marrow, the demonstration of tumor spread beyond the bony cortex without disruption of the outline of the diseased bone may favor the diagnosis of lymphoma more than that of metastases or multiple myeloma.
Androulakis N, Kourousis C, Dimopoulos MA, Samelis G, Kakolyris S, Tsavaris N, Genatas K, Aravantinos G, Papadimitriou C, Karabekios S, et al. Treatment of pancreatic cancer with docetaxel and granulocyte colony- stimulating factor: A multicenter phase II study. Journal of Clinical Oncology [Internet]. 1999;17(6):1779 - 1785. WebsiteAbstract
Purpose: To determine the efficacy and tolerance of single-agent docetaxel and granulocyte colony-stimulating factor in patients with advanced pancreatic cancer. Patients and Methods: Thirty-three chemotherapy-naive patients (median age, 65 years) with histologically confirmed pancreatic cancer were treated, after appropriate premedication, with docetaxel (100 mg/m2) and granulocyte colony-stimulating factor (150 μg/m2/d subcutaneously days 2 through 10) every 3 weeks. World Health Organization performance status was 0 to 1 in 28 patients (85%) and 2 in 5 patients (15%). Twenty-nine patients had stage III and IV disease. Results: One complete response (3%) and one partial response (3%) were observed for an overall response rate of 6% (95% confidence interval, 2.1% to 14.2%). Nineteen patients (58%) had stable disease and 12 (36%) had progressive disease. The duration of the two objective responses was 10 and 28 weeks, and the median time to tumor progression was 20 weeks. The median overall survival was 36 weeks. The actuarial 1-year survival was 36.4%. The performance status improved in seven of 21 assessable patients (24%) and pain improved in 14 of 21 (67%) assessable patients; five patients (29%) experienced weight gain during treatment. Disease-related asthenia, anorexia, vomiting, and diarrhea improved in 29%, 15%, 67%, and 47% of the assessable patients, respectively. Serum concentrations of CA 19-9 were decreased by more than 50% in seven patients (35%). Grade 3 and 4 neutropenia occurred in four patients (12%) and eight patients (24%), respectively, with two episodes of febrile neutropenia. There were no treatment-related deaths. Grade 3/4 asthenia occurred in three patients. Conclusion: Although docetaxel has a marginal objective activity in pancreatic cancer, it seems to have an important effect on tumor growth control, conferring a clinical benefit.
Georgoulias V, Kouroussis C, Androulakis N, Kakolyris S, Dimopoulos M-A, Papadakis E, Bouros D, Apostolopoulou F, Papadimitriou C, Agelidou A, et al. Front-line treatment of advanced non-small-cell lung cancer with docetaxel and gemcitabine: A multicenter phase II trial. Journal of Clinical Oncology [Internet]. 1999;17(3):914 - 920. WebsiteAbstract
Purpose: To evaluate the tolerance and efficacy of the combination of docetaxel and gemcitabine in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods: Fifty-one chemotherapy-naive patients with NSCLC were treated with gemcitabine 900 mg/m2 intravenously on days 1 and 8 and docetaxel 100 mg/m2 intravenously on day 8 with granulocyte colony-stimulating factor (150 μg/m2, subcutaneously) support from day 9 to day 15. Treatment was repeated every 3 weeks. Results: The patients' median age was 64 years. The World Health Organization performance status was 0 to 1 in 39 patients and 2 in 12 patients. Fifteen patients (29%) had stage IIIB disease, and 36 (71%) had stage IV; histology was mainly squamous cell carcinoma (59%). A partial response was achieved in 19 patients (37.5%; 95% confidence interval, 24% to 50%); stable disease and progressive disease were each observed in 16 patients (31.4%). The median duration of response and the time to tumor progression were 5 and 6 months, respectively. The median survival was 13 months, and the actuarial 1-year survival was 50.7%. Grade 4 anemia and thrombocytopenia were rare (2%). Four patients (8%) developed grade 3 or 4 neutropenia, and all were complicated with fever; there was no treatment-related death. Grade 3 or 4 diarrhea occurred in three patients (6%), grade 2 or 3 neurotoxicity in four patients (8%), grade 2 or 3 asthenia in 10 patients (20%), and grade 2 or 3 edema in 10 patients (20%). Conclusion: The combination of docetaxel/gemcitabine is well tolerated, can be used for outpatients, and is active for the treatment of advanced NSCLC. This treatment merits further comparison with other cisplatin- or carboplatin-based combinations.
Moulopoulos LA, Karvouni E, Kehagias D, Dimopoulos MA, Gouliamos A, Vlahos L. MR imaging of complex tail-gut cysts. Clinical Radiology [Internet]. 1999;54(2):118 - 122. WebsiteAbstract
Retrorectal-cyst hamartomas (RCH) are rare developmental tail-gut cystic tumours of the retrorectal space, which occasionally undergo malignant transformation. We describe the magnetic resonance imaging (MRI) findings in two patients with RCH and in a third patient with unclassified sarcoma arising from a RCH. The RCH were hypointense or hyperintense on T1-weighted images and hyperintense on T2-weighted images; they did not enhance and they contained multiple septations. A solid component in the periphery of one cyst was markedly hypointense on T2-weighted images in keeping with fibrous material. The sarcoma arising from the wall of the RCH enhanced and was of intermediate signal intensity on all sequences. MR may help establish the diagnosis of RCH if an unenhanced cystic tumour is discovered in the retrorectal space and it can help detect those rare cases of malignant transformation of these developmental tumours.
Ha CS, Kavadi V, Dimopoulos MA, Hagemeister FB, Osborne BM, Fuller LM, Smith TL, Hess MA, McLaughlin PW, Cabanillas FF, et al. Hodgkin's disease with lymphocyte predominance: Long-term results based on current histopathologic criteria. International Journal of Radiation Oncology Biology Physics [Internet]. 1999;43(2):329 - 334. WebsiteAbstract
Purpose: To define the disease course, therapeutic strategies, patterns and rates of relapse and causes of death for patients with Hodgkin's disease with lymphocyte predominance (LPHD) and to assess prognostic factors including nodular and diffuse histologic patterns. Patients and Methods: The records of all previously untreated patients with LPHD who received initial treatment at the University of Texas M.D. Anderson Cancer Center (UTMDACC) from 1960 through 1992 were reviewed. Clinical and histopathologic characteristics, specifically nodular and diffuse LPHI), and treatment groups were assessed by overall and relapse-free survival, patterns of relapse, and causes of death. Results: Of 70 patients, 58 (83%) had nodular LPHD and 12 (17%) had a diffuse pattern: clinical characteristics were similar between the two subtypes. The median age of all patients was 25 years, 79% were male, 96% presented with stage I or II disease and 93% were free of B symptoms. Laparotomy (23 patients) failed to upstage any patient with a negative lymphogram. With a median follow-up of 12.3 years for alive patients, 19 (27%) patients have relapsed. All 3 relapses among the patients with diffuse subtype occurred within 3 years while 9 of 16 relapses occurred after 5 years with nodular subtype. However, we did not detect any statistically significant difference in relapse free survival or survival between the subtypes in our patient population. There was some suggestion that patients aged 40 and older experienced shorter survival; no other pretreatment characteristics were noted to be associated with relapse free survival or survival. Though there were no relapses within the radiation fields, no effect of extent of radiation therapy on relapse rate was observed. Thirteen (19%) patients have died, 6 (8.6%) of whom succumbed to LPHD. Two patients developed diffuse large cell lymphoma. Conclusions: Patients with LPHD usually present with localized and asymptomatic disease. Laparotomy is unnecessary if the lymphogram is negative. Nodular histology occurred in the majority of patients. Though all relapses from diffuse subtype occurred within 3 years in contrast to some late relapses observed for nodular subtype, there was no statistically significant difference in relapse free survival or survival between the subtypes. The extent of irradiation had no effect on relapse free survival or survival. We could not find any evidence that LPHD should be treated any different from the classical Hodgkin's disease at this point despite suggestions that it be classified as a non- Hodgkin's B-cell lymphoma.
Athanassiadou P, Petrakakou E, Liossi A, Nakopoulou L, Zerva C, Dimopoulos A, Athanassiades P. Prognostic significance of p53, bcl-2 and EGFR in carcinoma of the endometrium. Acta Cytologica [Internet]. 1999;43(6):1039 - 1044. WebsiteAbstract
OBJECTIVE: To evaluate the part played by several parameters in the prognosis of patients with endometrial carcinoma. STUDY DESIGN: Eighty imprint smears from fresh endometrial tumor specimens were studied immunocytochemically for the expression of p53, bcl-2 and epidermal growth factor receptor. Also, the presence of estrogen receptor (ER) and progesterone receptor (PR) in the tumor tissue was measured. The data obtained were related to survival, and associations were sought between the parameters studied. RESULTS: Strong associations were found between advanced stage, high grade, lymph node metastases at diagnosis, nonendometrioid histology and p53 expression with poor survival. Bcl-2 expression was associated with good five-year survival. ER expression was associated marginally with good five-year survival, but PR expression was not. A strong association was found between p53 and advanced disease, stage and lymph node metastases at diagnosis. An association between EGFR positivity and survival was not found. CONCLUSION: p53 Expression of uterine tumors is an independent and strong indicator of poor prognosis. Even patients with stage I and II disease at surgery who have p53-positive tumors must be considered at high risk.
Papadimitriou CA, Sarris K, Moulopoulos LA, Fountzilas G, Anagnostopoulos A, Voulgaris Z, Gika D, Giannakoulis N, Diakomanolis E, Dimopoulos MA. Phase II trial of paclitaxel and cisplatin in metastatic and recurrent carcinoma of the uterine cervix. Journal of Clinical Oncology [Internet]. 1999;17(3):761 - 766. WebsiteAbstract
Purpose: Both paclitaxel and cisplatin have moderate activity in patients with metastatic or recurrent cancer of the cervix, and the combination of these two agents has shown activity and possible synergism in a variety of solid tumors. We administered this combination to patients with metastatic or recurrent cervical cancer to evaluate its activity. Patients and Methods: Thirty-four consecutive patients were treated on an outpatient basis with paclitaxel 175 mg/m2 administered intravenously over a 3-hour period followed by cisplatin 75 mg/m2 administered intravenously with granulocyte colony-stimulating factor support. The chemotherapy was administered every 3 weeks for a maximum of six courses. Results: Sixteen patients (47%; 95% confidence interval, 30% to 65%) achieved an objective response, including five complete responses and 11 partial responses. Responses occurred in 28% of patients with disease within the radiation field only and in 57% of patients with disease involving other sites. The median duration of response was 5.5 months, and the median times to progression and survival for all patients were 5 and 9 months, respectively. Grade 3 or 4 toxicities included anemia in 18% of patients and granulocytopenia in 15% of patients. Fifty-three percent of patients developed some degree of neurotoxicity; 21% of cases were grade 2 or worse. Conclusion: The combination of paclitaxel with cisplatin seems relatively well tolerated and moderately active in patients with metastatic or recurrent cervical cancer. The significant incidence of neurotoxicity is of concern, and alternative methods of administration of the two agents could be evaluated. Then, further study of this combination, alone or with the addition of other active agents, is warranted.
Dimopoulos MA, Bakoyannis C, Georgoulias V, Papadimitriou C, Moulopoulos LA, Deliveliotis C, Karayannis A, Varkarakis I, Aravantinos G, Zervas A, et al. Docetaxel and cisplatin combination chemotherapy in advanced carcinoma of the urothelium: A multicenter phase II study of the Hellenic Cooperative Oncology Group. Annals of Oncology [Internet]. 1999;10(11):1385 - 1388. WebsiteAbstract
Purpose: Both docetaxel and cisplatin have moderate activity in patients with advanced urothelial cancer. We performed a multicenter phase II study in order to assess the efficacy and toxicity of the combination of these two agents in patients with advanced carcinoma of the urothelium. Patients and methods: Sixty-six patients not amenable to curative surgery or irradiation were enrolled onto this cooperative group study and treated on an outpatient basis with docetaxel 75 mg/m2 followed by cisplatin 75 mg/m2, both administered intravenously. Granulocyte-colony stimulating factor was administered subcutaneously at a dose of 5 μg/kg daily from day 5 until resolution of neutropenia. The chemotherapy was administered every three weeks for a maximum of six courses in patients without evidence of progressive disease. Results: Thirty-four of sixty-six patients (52%, 95% confidence interval 40%-64%) demonstrated objective responses, with eight achieving clinical complete responses and twenty-six partial responses. A multivariate logistic regression analysis indicated that the patients most likely to respond were those without lung metastasis and without weight loss before treatment. The median duration of response was 6.1 months and the median times to progression and survival for all patients were 5 and 8 months, respectively. Absence of anemia, of liver metastases and of weight loss correlated with longer survival. Grade ≥3 toxicities included granulocytopenia in 33% of patients, anemia in 14%, diarrhea in 13% and emesis in 7% of patients. Conclusion: The combination of docetaxel and cisplatin appeared relatively well tolerated and moderately active in patients with advanced urothelial cancer. The patients most likely to benefit were those without weight loss and without lung or liver metastases.
Dimopoulos MA, Galani E, Matsouka C. Waldenstrom's macroglobulinemia. Hematology/Oncology Clinics of North America [Internet]. 1999;13(6):1351 - 1366. WebsiteAbstract
Waldenstrom's macroglobulinemia is an unusual low-grade lymphoplasmacytic lymphoma characterized by the production of monoclonal IgM. The clinical manifestations associated with WM can be classified as those related to direct tumor infiltration, by the amount and specific properties of circulating IgM, and by the deposition of IgM in various tissues. Asymptomatic patients should be followed without treatment. The management of the disease relies on the administration of systemic chemotherapy to reduce tumor load and on the application of plasmapheresis to remove circulating IgM. Standard treatment consists of oral chlorambucil, which induces response in at least 50% of patients, resulting in a median survival of approximately 5 years. Nucleoside analogues (cladribine, fludarabine) are effective in most previously untreated patients. These agents are the treatment of choice for patients with disease resistant to alkylating agents. New treatment approaches include high-dose therapy with stem-cell support and administration of monoclonal anti-CD20 antibodies.
Dimopoulos MA, Kiamouris C, Moulopoulos LA. Solitary plasmacytoma of bone and extramedullary plasmacytoma. Hematology/Oncology Clinics of North America [Internet]. 1999;13(6):1249 - 1257. WebsiteAbstract
A small proportion of patients with plasma cell myeloma have a solitary plasmacytoma of bone. Strict staging criteria, including normal MR imaging studies of the axial skeleton and the long bones and absence of monoclonal plasma cells detected by flow cytometry or PCR, are required for diagnosis. Radiotherapy at a dose of 4500 cGy is required to eradicate the local tumor. Many patients enjoy prolonged disease-free survival, but the incidence of systemic relapse is high. It is expected, however, that if strict diagnostic criteria are applied some patients may be cured. Extramedullary plasmacytoma is an even rarer plasma cell disease which usually occurs in the head and neck area. Careful microscopic and immunohistochemical studies are required for the correct diagnosis, because this disease can be confused with other malignancies, particularly lymphomas. The treatment of choice is radiotherapy which, in cases of head and neck plasmacytomas, should encompass the adjacent lymph nodes. Most patients with extramedullary plasmacytoma can be cured, and fewer than 30% develop a distant failure in the form of multiple myeloma or multiple extramedullary tumors.