Aggressive Combination Chemotherapy Research Articles

Clinicopathological features and management of immunoproliferative small intestinal disease and primary small intestinal lymphoma in pakistan

This study was performed to confirm the existence of immunoproliferative small intestinal disease (IPSID) in Pakistan. Clinicopathological features of 12 patients with histologically confirmed disease were analysed. Patients were mostly young males with median age of 24.6 years. Two thirds belonged to poor socioeconomic class. Main presenting features were chronic diarrhoea and weight loss. Eleven patients had radiologic evidence of malabsorption syndrome. Endoscopic findings of mucosal thickening, edema, and flattened villi were present in the majority. Patients had both secretory and non-secretory types of disease. Six patients presented with stage A disease. Four responded to antibiotics or steroids, although mucosal abnormalities persisted in three. Two stage A patients evolved into stage C disease, one was lost to follow-up, the other is alive with disease. Three patients presented with stage B disease. Two responded completely to chemotherapy, the third refused treatment and expired after 16 months. Three patients had stage C disease at diagnosis. They received aggressive combination chemotherapy and remain in complete remission with a median follow-up of 2.2 years. This is the first series of patients with IPSID reported from Pakistan. Clinicopathological features and therapeutic results are consistent with the experience elsewhere. Increased awareness may result in early diagnosis and better management.

Long-Term Remission of Previously Resistant Choriocarcinoma with a Combination of Etoposide, Ifosfamide, and Cisplatin

A 30-year-old white female was diagnosed with gestational trophoblastic disease in 1981. Despite an original World Health Organization score of 4 and initial aggressive combination chemotherapy, she was treated over a 9-year period with multiple chemotherapy agents and had undergone several operative procedures to remove metastatic lesions for persistent disease. Long-term remission has now been obtained after four courses of etoposide, ifosfamide, and cisplatin.

Etoposide/vincristine-based chemotherapy with or without carboplatin in extensive-stage small cell lung cancer: A prospective randomized phase III trial: Gatzemeier U, Pawel JV, Laumen R, Hossfeld DK, Neuhauss R. Department of Thoracic Oncology, Pneumology/Thoracic Surgery Center, Grosshansdorf Hospital, D 2070 Grosshansdorf/Hamburg. Semin Oncol 1994;21:Suppl 6:31–35

In the treatment of small cell lung cancer, carboplatin/etoposide/vincristine (CEV) is one of the most active regimens. In contrast, the etoposide/vincristine (EV) combination also has produced acceptable results in patients with extensive disease. To evaluate the efficacy and survival of patients treated with EV in comparison to those treated with more intensive CEV chemotherapy, a prospective, randomized, phase III trial was performed. The protocol for the treatment groups was as follows: treatment A (156 patients): carboplatin 300 mg/m2 day I, etoposide 140 mg/m2 days 1 through 3, and vincristine 1.4 mg/m2 days 1, 8, and 15; and treatment B (161 patients): etoposide 200 mg/m2 days 1 through 3 and vincristine 1.4 mg/m2 days 1 and 8. Chemotherapy cycles in each treatment arm were repeated every 4 weeks. Doses were reduced by 20% when hematologic or nonhematologic toxicity (grade 4) occurred. In all, 317 evaluable patients were treated. The overall response rate for patients treated with CEV was 79.8% compared with 59.8% for those treated with EV (P < .001). The median length of survival was 10 months for CEV-treated patients compared with 9 months for EV-treated patients (P = .19). Based on long-term survival rates, there was an advantage for the CEV-treated patients if they had good performance status, were younger than 60 years, had no distant metastases, and achieved a complete response to first-line therapy. We conclude that patients with poor prognostic factors (ie, poor performance status, multiple distant metastases, and less than partial response to the first cycle of chemotherapy) should appropriately be treated with the less aggressive two-drug combination chemotherapy. On the other hand, patients with good prognostic factors should be treated as aggressively as possible, and they will benefit from the more aggressive induction chemotherapy.

Intravascular lymphomatosis: a clinicopathologic study of 10 cases and assessment of response to chemotherapy.

We report a clinicopathologic study of 10 cases of intravascular lymphomatosis (IVL) seen at a single institution, and assess the response to chemotherapy in these patients, as well as those collected from a literature review. The clinical, pathologic, and immunophenotypic features of 10 cases of IVL diagnosed at the Johns Hopkins Hospital since 1977 were studied. Follow-up information was obtained in each case by consultation with the treating physician. In addition, cases of IVL reported previously in which patients were treated with chemotherapy and for which follow-up data were available at the time of publication were reviewed. In the present series of 10 cases, the most common clinical features were fever of unknown origin (FUO), mental status changes, and rash. Diagnostic specimens were obtained from a variety of sources, including brain, skin, prostate, liver, kidney, and gallbladder. All of the four patients treated with combination chemotherapy are alive and two have achieved long-term survival (48 and 45 months, respectively); the remaining two are alive and in complete remission (CR) after short follow-up duration of 6 months. Among 35 patients reported in the literature who received chemotherapy (including four from this series), 43% attained a CR and were free of disease at the time of publication. None of the three patients in our series who received localized therapy (surgery with or without radiation therapy) is alive (mean survival duration, 9 months). For the three patients diagnosed at postmortem examination, the mean interval between onset of symptoms and death was 3 months, and disease was widespread. These findings suggest that IVL represents a high-grade non-Hodgkin's lymphoma (NHL) with a propensity for systemic dissemination, and that CR and long-term survival may result in patients treated with aggressive combination chemotherapy.

Endodermal sinus tumor of the ovary: review of 10 cases.

Endodermal sinus tumors are rare but highly malignant neoplasms of children and young adults. In all, only about 200 cases have been reported in the literature. Ten patients with endodermal sinus tumor of the ovary who were treated at Jackson Memorial Hospital from 1977 to 1989 were retrospectively reviewed. The median age of these patients was 24.7 years. The most common presenting symptom was abdominal pain, occurring in all our patients. Nine of the 10 patients received combination chemotherapy; all but one survived and are currently well. The patient who received no chemotherapy died. Eight of the ten patients are alive and well. The roles of alpha-fetoprotein monitoring, second-look laparotomy, and conservative surgery are discussed. The need for aggressive combination chemotherapy for this tumor is confirmed by this study.

Choriocarcinoma in a term placenta with maternal metastases

Choriocarcinoma of the nonmolar placenta is presumptively a rare entity and is usually associated with widespread maternal metastases at the time of diagnosis. Nonmetastatic disease goes unrecognized and undiagnosed because placental carcinoma can be limited to a few villi, and grossly evident disease is often misinterpreted as a placental infarct. The optimal treatment for patients with choriocarcinoma of the placenta is not known but aggressive combination chemotherapy is suggested for patients with metastatic disease. Historically, the prognosis for both mother and infant has been poor.

Primary non-Hodgkin's lymphomas of the paranasal sinuses and nasal cavity. A report of 18 cases with stage IE disease.

During a 26-year period (1961-1987), a total of 18 patients with primary non-Hodgkin's lymphoma (NHL) of the paranasal sinuses and nasal cavity received radiation therapy at (University of California at Los Angeles) UCLA Medical Center. At the time of diagnosis and using the available diagnostic methods, none of these patients had clinically detectable disease beyond the paranasal sinuses. All 18 patients were staged IE by the Ann-Arbor system. When the patients were staged according to the AJC staging system from epithelial tumors, half presented with advanced T3-4 disease. Diffuse histiocytic lymphoma was the most common histology (eight cases) and maxillary sinus, the most common site of origin (11 cases). All nine T1-2 tumors received radiation therapy alone, while radiation and chemotherapy was used in seven of nine advanced T3-4 staged tumors. The mean follow-up was 71 months. At last follow-up, eight of nine T1-2 patients were rendered disease-free. In contrast, only four of nine T3-4 patients had long-term disease-free survival. Seventy-five percent of the failure occurred within 2 years. Radiation therapy alone achieves high local control in small tumors (T1-2), while large tumors (T3-4) require aggressive combined treatment, i.e., radiation and chemotherapy.

Treatment and prognosis of orbital non-Hodgkin's lymphomas.

Twenty patients with orbital lymphomas were treated and followed over a 14-year period. Ten of these patients had well-differentiated lymphocytic lymphoma (WDL), and all of them were clinical stage IE. Five patients had nodular poorly differentiated lymphocytic lymphomas (NPDL), three patients had diffuse histiocytic lymphomas (DHL), one had nodular mixed-cell lymphoma, and one had diffused mixed-cell lymphoma. The patients with WDL received local radiation therapy, and all of them entered completed remissions. The projected survival at 10 years was 100% for these patients. The patients with low-grade lymphomas with advanced disease were treated with chlorambucil and prednisone or cytoxan and vincristine. The patients with high-grade lymphomas received treatment with methotrexate, cyclophosphamide, doxorubicin, vincristine, bleomycin, dexamethasone (mBACOD) or cyclophosphamide, vincristine, methotrexate, cytosine arabinoside, leucovorin (COMLA). The overall survival estimate for all patients was 63% at 10 years. The disease-free survival was 49% at 10 years. The patients with high-grade lymphomas had a poor prognosis, with no survivors after 4 years. This study suggests that patients with WDL usually present with localized disease to the involved orbit, and have an excellent prognosis with radiation therapy alone. Patients with high-grade orbital non-Hodgkin's lymphomas have a poor outcome despite use of aggressive combination chemotherapy regimens.

Aggressive chemotherapy for acute leukemia relapsed after bone marrow transplantation: a second chance?

Eight patients, 5 with acute non lymphoid leukemia and 3 with lymphoid leukemia, were treated at relapse after bone marrow transplantation (BMT; 4 autologous BMT and 4 allogeneic BMT). Of these, 2 relapsed within 3 months after BMT (2 allogeneic BMT) and 6 (2 allogeneic and 4 autologous BMT) after more than 9 months after BMT. The 2 patients relapsing early showed no response to treatment and died. Five out of 6 patients relapsing late achieved complete remission (4 of them with intensive chemotherapy). Four patients are currently alive. Aggressive combination chemotherapy can produce long-term survival in selected patients relapsed after BMT.

Chemotherapy for recurrent or metastatic carcinoma of the nasopharynx. A review of the princess margaret hospital experience

There is little information about the ability of chemotherapy to achieve palliation for patients with recurrent or metastatic carcinoma of the nasopharynx. Therefore, the authors reviewed the records of all patients who had received chemotherapy for this disease at the Princess Margaret Hospital between 1970 and 1989. Seventy patients were identified who had measurable disease and had not received prior systemic therapy. Forty patients received single agents or nonaggressive drug combinations, most of them before 1980. There were three complete responses (CR) and seven partial responses (PR) among this group for a response rate of 25% (95% confidence limits, 13% to 41%). Thirty patients received either drug combinations that were active in aggressive lymphomas or cisplatin-based combinations. There were 7 CR and 14 PR among this group for a response rate of 70% (95% confidence limits, 51% to 85%). Two patients who were treated aggressively are still alive and in complete remission at 3 and 12 years. This type of retrospective review cannot exclude bias caused by patient selection. However, in the absence of randomized trials, the authors suggest the following: (1) carcinoma of the nasopharynx should be considered a malignant neoplasm that is distinct from squamous cell cancer in other sites of the head and neck; and (2) selected patients with recurrent or metastatic carcinoma of the nasopharynx should receive aggressive combination chemotherapy.

Low-dose total body irradiation versus combination chemotherapy for lymphomas with follicular growth pattern

The treatment of Non-Hodgkin's lymphomas with follicular growth pattern and advanced stage of disease remains controversial. Treatments varying from no initial treatment up to aggressive combination chemotherapy have been advocated. The EORTC Lymphoma Cooperative Group has performed a randomized prospective trial comparing short duration low dose total body irradiation (TBI) vs combination chemotherapy (CHVmP) + consolidation radiotherapy. Ninety-three patients were entered; of 84 evaluable patients, 44 received TBI and 40 CHVmP. Complete remission (CR) rates were 36% - TBI and 55% - CHVmP, but overall response rates were identical, 76 versus 69%. No significant difference in freedom from progression or survival was observed. No unexpected toxicity was seen. Although numbers are small, we cannot conclude that aggressive combination chemo-radiotherapy resulted in a better survival. Our analysis confirms that there is a constant risk of relapse. Other approaches should be explored if survival benefit is the ultimate goal in treatment of this patient population.

Testicular Lymphoma - The Need for a New Approach

Thirteen cases of malignant lymphoma of the testis were referred to the Queensland Radium Institute between 1975 and 1989. The age varied from 43 years to 84 years and the histology was intermediate to high grade in all cases. Seven patients had Stage I/II and 6 had Stage III/IV. The 4 year survival was only 16%. Half of the relapses were systemic, 1 was in the para-aortic nodes (unirradiated) and 2 were in the opposite testicle. Adjuvant radiotherapy to para-aortic nodes and mild chemotherapy have produced disappointing results. A new approach using aggressive combination chemotherapy and adjuvant scrotal irradiation is proposed for early stage disease.

YOLK SAC TUMOUR OF THE ANTERIOR MEDIASTINUM

Two cases of yolk sac tumour involving the anterior mediastinum in two young Chinese males are described. The tumour in both patients could only be partially debulked, and they died within a few months despite multiple chemotherapy. The importance of early diagnosis, radical surgery and aggressive combination chemotherapy in prolonging the period of survival of such patients is emphasized. Serum alpha-fetoprotein should be determined in every patient, especially a young male adult, who presents radiologically with a hilar mass.

Peripheral T Cell Lymphoma: an Overview.

Peripheral T cell lymphoma (PTCL) is a term that encompasses a wide range of histological subtypes of Non-Hodgkin's lymphoma which arise from mature or post-thymic T lymphocytes. These tumours account for 10-20% of all cases of non-Hodgkin's lymphoma in the Western World. With the exception of HTLV1 associated lymphoma, there is little evidence that the incidence of PTCL is increasing. However, the diagnosis of PTCL is being made with greater frequency due to both an increased awareness of the entity and the more widespread use of phenotypic and genotypic studies for characterising lymphoid populations. The clinical course of PTCL is variable and less well documented than that for B cell lymphomas. As with B cell lymphomas, stage of disease is a major determinant of prognosis although the importance of histological subtype is still uncertain. Aggressive combination chemotherapy may result in complete remission and perhaps long term survival, but further prospective studies are urgently needed.

Angiotropic large cell lymphoma (ALCL): Morphological, immunohistochemical and genotypic studies with analysis of previous reports

The entity 'angioendotheliomatosis proliferans systemisata' was first described 28 years ago as a cutaneous small vessel neoplasm of presumed endothelial origin. Since then, 101 similar cases have been reported under a variety of different names, most with systemic as well as cutaneous lesions, and a lymphoid histogenesis of the tumour cell is now favoured. Review of these cases has shown a characteristic clinical presentation with predominant neurological and dermatological features, although the diagnosis was made at autopsy in 53 per cent of patients. Most therapeutic regimens have proved ineffective with a median survival of 5 months from date of clinical presentation. Aggressive combination chemotherapy can produce complete and lasting remission and a partial response to steroids is sometimes seen. We have examined a case of this condition showing unusual clinical features. Immunohistochemical studies confirm the lymphoid origin of the tumour cells with B cell phenotype. Antigen receptor gene rearrangement studies indicate the presence of the same clonal population of B cells in multiple sites. We suggest that the term 'angioendotheliomatosis proliferans systemisata' should be dropped and support the use of 'angiotropic large cell lymphoma' to describe this unusual condition.

非ホジキンリンパ腫の放射線治療

Treatment results of 256 patients with histologically proven non-Hodgkin's lymphomas (NHL), clinical stages I and II, treated by radiotherapy alone (113 patients) or in combination with systemic chemotherapy (143 patients), were retrospectively analyzed in order to clarify the efficiency of radiotherapy in the control of NHL. Sixtyfour patients had Waldeyer's ring lesion with or without cervical lymphadenopathy and the rest of the patients had cervical lesions primarily with or without other lymphadenopathy above diaphragm.As for the patients with NHL involving Waldeyer's ring, all of 17 patients with stage I and 9 of 14 patients with limited type of stage II, which were defined as having hemilateral cervical lymphadenopathy less than 4cm in diameter as well as primary lesion of the Waldeyer's ring, were treated by radiotherapy alone. Five-year survival rates were 100% and 88%, respectively. They could be treated safely by radiotherapy alone. Five-year survival rate of 12 patients with advanced stage II treated mainly by CHOP chemotherapy with adjuvant radiotherapy was 83%, while that of 21 patients with the corresponding stage treated by radiotherapy alone or by radiotherapy with adjuvant non-ADM containing chemotherapy was only 9.5%.Among 129 patients with stage I NHL involving primarily cervical lymph nodes, 37 patients with all cell type of follicular lymphomas and diffuse lymphoma, small cell type and 26 patients with other diffuse lymphomas, whose maximum tumor size was less than 4cm in diameter had excellent prognoses (10 year survival: more than 85%), regardless of using systemic combination chemotherapy. It was considered that they could also be treated by radiotherapy alone. On the other hand, 57 patients with diffuse lymphomas excluding small cell type, whose tumor size was 4cm in diameter or more had poorer survival rate (5-year survival rate: 54%), when they were treated by radiotherapy alone. Among 63 patients with stage II nodal NHL, treatment results of 57 patients with diffuse lymphomas excluding small cell type were poor (5-year survival rate: 30%), especially those of large cell type. They should be treated with aggressive combination chemotherapy.

Weekly doxorubicin in the treatment of metastatic breast carcinoma.

The introduction of aggressive combination chemotherapy has not been accompanied by any significant prolongation of survival in metastatic breast carcinoma. Hence, there is a need of less toxic but--in terms of palliation--effective chemotherapeutic regimens. This paper concerns 50 patients with progressive metastatic breast carcinoma who were treated with weekly bolus injections of doxorubicin (15-20 mg). All patients were followed until disease progression. A partial response with a mean duration of 6 months was achieved in 7 patients (14%). In addition, stabilization of disease was observed in 24 patients (48%) during 2-34 months. The toxicity was generally mild. It is concluded that weekly doxorubicin with fairly low doses is a moderately effective treatment in stage IV breast carcinoma. It is devoid of severe toxicity which makes it useful even in old and debilitated patients.

Angiocentric immunoproliferative lesions: a clinicopathologic spectrum of post-thymic T-cell proliferations

Twenty-three patients with angiocentric immunoproliferative lesions (AILs) including angiocentric lymphoma were evaluated clinically and pathologically. Pathologic subclassification performed without knowledge of the clinical outcome divided the cases into three histologic grades on the basis of cellular atypia and degree of inflammatory background. Immunophenotypic studies of lesions from six patients demonstrated a mature T-cell phenotype with a predominance of CD4-positive cells. Abnormalities of antigenic phenotype were demonstrated in only one case, classified as grade III. That tumor also demonstrated a clonal rearrangement of the T beta gene. Progression to malignant lymphoma following initial immunosuppressive therapy with cyclophosphamide and prednisone occurred in three of nine patients with grade I lesions and four of six patients with grade II lesions. The supervening lymphomas were usually refractory to subsequent aggressive chemotherapy, with only one patient achieving a complete remission. In contrast, seven of eight patients with grade III lesions achieved a complete remission with aggressive combination chemotherapy, two of whom also received supplemental radiation therapy. These studies support the concept that the AILs represent a spectrum of post-thymic T- cell proliferations. The single most important prognostic indicator for ultimate survival is achievement of an initial complete remission. Patients treated initially with conservative chemotherapy may be compromised in their ability to achieve a complete remission if they progress to a higher grade lesion.

Angiocentric Immunoproliferative Lesions: A Clinicopathologic Spectrum of Post-Thymic T-Cell Proliferations

Twenty-three patients with angiocentric immunoproliferative lesions (AILs) including angiocentric lymphoma were evaluated clinically and pathologically. Pathologic subclassification performed without knowledge of the clinical outcome divided the cases into three histologic grades on the basis of cellular atypia and degree of inflammatory background. Immunophenotypic studies of lesions from six patients demonstrated a mature T-cell phenotype with a predominance of CD4-positive cells. Abnormalities of antigenic phenotype were demonstrated in only one case, classified as grade III. That tumor also demonstrated a clonal rearrangement of the T beta gene. Progression to malignant lymphoma following initial immunosuppressive therapy with cyclophosphamide and prednisone occurred in three of nine patients with grade I lesions and four of six patients with grade II lesions. The supervening lymphomas were usually refractory to subsequent aggressive chemotherapy, with only one patient achieving a complete remission. In contrast, seven of eight patients with grade III lesions achieved a complete remission with aggressive combination chemotherapy, two of whom also received supplemental radiation therapy. These studies support the concept that the AILs represent a spectrum of post-thymic T-cell proliferations. The single most important prognostic indicator for ultimate survival is achievement of an initial complete remission. Patients treated initially with conservative chemotherapy may be compromised in their ability to achieve a complete remission if they progress to a higher grade lesion.

The non-Hodgkin's lymphomas: Pathology, staging, treatment

The non-Hodgkin's lymphomas include a broad range of neoplasms derived from the T cells and B cells and their precursors in the lymphoid system. Although they are not among the most common cancers, the lymphomas have engendered a great deal of interest among researchers because of their interesting biology and responsiveness to therapy. The non-Hodgkin's lymphomas include at least ten major subtypes of diseases with different morphologic characteristics and clinical behavior. Based upon survival characteristics, it is convenient to divide the lymphomas into three broad categories, low grade, intermediate grade, and high grade. The low grade lymphomas usually arise in middle age or older individuals (median age, 55 years). They are derived from B cells and often have a folicular architectural pattern. They usually present with advanced stages of disease, often by virtue of bone marrow involvement. Nevertheless, patients are usually asymptomatic and may even have spontaneous regressions of disease. These lymphomas are responsive to a broad range of therapies including irradiation, single agent or multiagent chemotherapy, or combined modality therapy. They also are affected by treatment with biologicals such as alpha interferon and monoclonal antibodies. Unfortunately, response to any of these therapies is often transient and relapse is common. The intermediate grade lymphomas include the common large cell lymphomas (follicular or diffuse) and diffuse mixed cell lymphoma. These lymphomas, together with the high grade immunoblastic lymphoma, are often grouped together for the development of management strategies. These lymphomas may be derived from B cells or T cells. They occur over a broader age range than the low grade lymphomas and they are much more aggressive in their natural behavior. Effective treatment programs have been developed for both limited and advanced clinical stages of disease. In limited disease, moderately intensive chemotherapy is often combined with involved field irradiation. In advanced stage disease, more aggressive combination chemotherapy programs are usually employed. From 40% to 80% of patients may be cured with these approaches, depending upon the initial extent of disease. Two types of high grade lymphoma-lymphoblastic and small noncleaved cell are particularly aggressive in their behavior. Lymphoblastic lymphoma is a T cell lymphoma that often arises in adolescent males and presents with a large mediastinal mass, marrow, and CNS involvement. It closely resembles acute lymphoblastic leukemia (ALL) and similarly intensive chemotherapy programs as are utilized in ALL may be successful in its management. Small noncleaved cell lymphoma is a B cell lymphoma that commonly presents with bulky disease, often involving intra-abdorninal sites such as the mesentery and gastrointestinal tract. This lymphoma has a short cell cycle time and rapid tumor doubling time and prompt initiation of treatment is indicated, in view of the poor prognosis for patients who present with either of these high grade lymphomas in the presence of adverse prognostic factors such as an elevated lactic dehydrogenase (LDH) or bone marrow involvement, investigational programs such as intensive systemic therapy combined with whole body irradiation, and bone marrow transplantation are being explored.