Methotrexate with citrovorum factor rescue as primary therapy for gestational trophoblastic disease

Methotrexate with citrovorum rescue (MTX-CF) was administered as primary treatment in 106 patients with gestational trophoblastic disease (GTD). Ninety-six patients (90.6%) achieved complete remission with MTX-CF and 77 of these patients (80.2%) required only one course of MTX-CF to attain remission. MTX-CF induced sustained remission in 89 (94.7%) of 94 patients with nonmetastatic GTD and in seven (59.3%) of 12 patients with low-risk metastatic GTD. Resistance to MTX-CF was more common in patients with disseminated disease and with pretreatment hCG titers greater than or equal to 50,000 milliIU/ml. Following MTX-CF, granulocytopenia, thrombocytopenia and hepatotoxicity was observed in only seven (6.6%), three (2.8%), and ten (9.4%) patients, respectively. MTX-CF should be the preferred primary treatment in nonmetastatic and low-risk metastatic GTD.     

Treatment of recurrent metastatic medulloblastoma with intensive chemotherapy and allogeneic bone marrow transplantation

We report here the first known case of a patient with recurrent metastatic medulloblastoma to achieve long-term disease-free survival following treatment with allogeneic bone marrow transplantation. A 27 year old white male with recurrent metastatic medulloblastoma involving lymph nodes, bone and bone marrow was treated with multi-agent chemotherapy followed by allogeneic bone marrow transplantation from an HLA-identical sibling donor. Morbidity was acceptable with moderate to severe mucositis in the immediate post transplant period and clinical grade I graft versus host disease of the skin controlled with modest doses of corticosteroids. The patient continues in unmaintained complete remission in excess of 28 months with a performance status of 100%. Allogeneic marrow transplantation following cytoreductive salvage chemotherapy is an aggressive strategy that may offer an improved likelihood of disease eradication and ultimate cure for poor prognosis patients with recurrent metastatic medulloblastoma.     

Management of breast cancer patients failing adjuvant chemotherapy with adriamycin-containing regimens

Sixty-two patients with breast cancer treated with Adriamycin-containing adjuvant chemotherapy developed recurrent disease. Four patients refused to take any form of systemic therapy at the time of relapse. Fifty-eight patients were managed with various treatment modalities, and of these 33 (57%) achieved on objective remission, 11 (19%) had stable disease and 14 patients (24%) did not respond to any form of therapy. Twenty-four patients received more than one treatment modality. Thirty-eight patients were treated with chemotherapy and 35 received endocrine therapy. Eight of 20 patients (40%) achieved objective remission upon retreatment with higher dose of 5-fluorouracil, Adriamycin, and cyclophosphamide at time of relapse, and seven of 18 patients (38%) treated with other chemotherapeutic agents showed objective remission. Fourteen of 35 patients (40%) achieved objective remission with hormonal therapies. The median survival from first relapse was 15 months for all patients, and was 25.7 months for responding patients. Survival was significantly longer in asymptomatic patients compared with those who were symptomatic from recurrent disease.     

Treatment outcome of recurrent cervical cancer

A total of 85 patients with recurrent cervical cancer were reviewed: 17 patients with recurrences were treated by radical surgery, 18 by radiotherapy, 29 by chemotherapy, and 21 cases received no further treatment. Survival was presented according to the site of recurrence and the mode of therapy. All patients were followed for a minimum of 24 months after recurrence. Of the total group, 14% are living without evidence of disease, 29% died of metastatic disease with no involvement in the pelvis, and 45% died of pelvic cancer. Overall, 22% were living more than 2 years, and only 2% lived over 5 years after recurrence. The NED (no evidence of disease) rate for radical surgery group was 47 and 44% for the radiotherapy group. There were no significant differences in median survival between the chemotherapy group and the no-treatment group (6.8 versus 4.8 months). New chemotherapy agents and adjuvant systemic therapy are discussed.     

Primary medical therapy for operable breast cancer

Fifty-seven patients with large but potentially operable primary breast cancer were treated with primary medical therapy rather than initial mastectomy, using chemotherapy (15) or endocrine therapy (42) with the tumour remaining in situ. Of patients treated with chemotherapy, one (7%) achieved a complete remission, and eight (53%) a partial response (overall response rate 60%). Only one patient had progressive disease while on chemotherapy. Of patients who received endocrine therapy, one (2%) achieved a complete response, and 19 (45%) a partial response (overall response rate 47%). Two patients progressed on endocrine therapy. Only 10 patients have so far had a subsequent mastectomy (18%), and 17 (30%) have had radiotherapy and/or conservative surgery. The rest are still on medical therapy.With a median follow-up of 19 months (range 6–42 months) only two patients have had a local recurrence after being disease-free and none have developed uncontrollable local recurrence. Eight (14%) have developed distant metastases and four (7%) have died of metastatic disease.Primary medical therapy may offer an effective alternative to mastectomy for patients with operable breast carcinomas too large for conservative surgery and merits further study.     

Survival Outcomes of Advanced and Recurrent Cervical Cancer Patients Treated with Chemotherapy: Experience of Northern Tertiary Care Hospital in Thailand

Chemotherapy is the primary treatment for advanced and recurrent cervical cancer. To evaluate the survival outcomes of chemotherapy and the prognostic factors in this setting, we conducted a retrospective study by reviewing the medical records of advanced and recurrent cervical cancer patients treated with systemic chemotherapy at our institute between January, 2008 and December, 2014. One hundred and seventy-three patients met the criteria with a mean age of 50.9 years. 4.1% of them were HIV positive. The most common initial stage was stage IVB (30.1%) and the most common histology was squamous cell carcinoma (68.6%). Ninety-two (53.2%) patients were previously treated with concurrent chemoradiation with 53% developing combined sites of recurrence. The median recurrence free interval was 16.7 months. Cisplatin 5 fluorouracil (5FU) (53.2%) was the most frequent first line chemotherapy followed by carboplatin paclitaxel (20.2%) with an objective response of 39.3%. Seventy-two patients received subsequent chemotherapy. The median overall survival of all studied patients was 13.2 months. Only a recurrence free interval of less than 12 months was an independent prognostic factor for survival outcome. In conclusion, chemotherapy treatment for advanced and recurrent cervical cancer patients showed modest efficacy with a shorter recurrence free survival less than 12 months as a significant poor prognosis factor.     

HCPT联合L-OHP方案治疗复发转移结直肠癌的近期临床疗效

背景与目的:虽然含氟尿嘧啶(5-fluarouracil,5-FU)联合方案是目前治疗结直肠癌的标准方案,但是作为二线治疗的疗效不高,探索新的替代方案显得十分必要。本研究拟应用羟基喜树碱(hydroxycampothecin,HCPT)联合草酸铂(oxaliplatin,L-OHP)方案治疗复发转移结直肠癌,并观察其近期疗效、不良反应及1年生存率。方法:47例经病理学检查证实的复发转移结直肠癌,采用HCPT L-OHP方案治疗86个周期,HCPT6mg/m2 NS500ml,静脉滴注d1～4;L-OHP130mg/m2 5%GS500ml,静脉滴注d1。每例治疗2个周期后进行近期临床疗效和不良反应评定,两次化疗间隔为3周。结果:38例可进行疗效评价,总有效率(CR PR)为36.8%(14/38)。化疗后KPS改善和显著改善者20例,占52.6%。白细胞下降59周期,占68.6%,其中Ⅲ～Ⅳ度白细胞下降18周期,占30.5%;腹泻48周期,占55.8%,其中Ⅲ～Ⅳ度腹泻18周期,占37.5%。1年生存率为40.0%,中位总生存期(medianoverallsurvival,mOS)和中位无进展生存期(medianprogressionfreesurvival,mPFS)分别为11.7和7.8个月。结论:HCPT L-OHP方案治疗一线化疗后复发的结直肠癌病例有较好的近期临床疗效,主要不良反应是白细胞下降和腹泻。     

Response of recurrent urachal cancer to gemcitabine and cisplatin therapy: a case report and literature review

Urachal cancer is a rare malignancy and the standard treatment is surgical resection. The prognosis of recurrent and metastatic urachal cancer is extremely poor because there is no established chemotherapy regimen. Here, the response of one patient with recurrent urachal cancer to combination chemotherapy of gemcitabine (GEM) and cisplatin (CDDP) (GC) is described. And the chemo- and radiotherapeutic regimens available for such patients are reviewed. A 67-year-old man diagnosed with stage IIIA urachal cancer underwent complete surgical resection. However, pelvic recurrence was detected on computed tomography (CT) 5 months after surgery. GC therapy was started immediately and resulted in a pronounced reduction in pelvic mass after three cycles. However, a follow-up CT scan taken 5 months later showed growth of the pelvic mass and new liver metastasis. He received GC therapy again, which resulted in reduction of the pelvic and liver metastatic masses after two cycles. However, the patient refused another course of GC therapy due to severe side-effects. Subsequent progression of the disease included spread in both regions, followed by death 16 months after recurrence. Various treatment strategies offer relatively long survival of patients with urachal cancer including those with recurrence and metastasis. Although further studies are necessary to determine its therapeutic efficacy, GC therapy may be a useful option in the treatment of urachal tumors, including recurrent tumours.     

A role for maintenance therapy in managing sarcoma

Despite the use of recommended chemotherapy regimens, patients with metastatic sarcomas have a poor prognosis. To date, the median overall survival for metastatic disease remains less than 18 months. First-line treatment of most metastatic sarcomas consists of chemotherapy with or without surgical excision of residual disease, followed by "watchful waiting" until disease progression or recurrence. According to the current treatment paradigm, recommended by United States and European clinical guidelines, chemotherapy is administered for a fixed number of cycles, and then a watchful waiting approach is taken once a best response is achieved. Single-agent doxorubicin remains the standard for treatment of most soft-tissue sarcomas (STS), as combination and dose-intense regimens have largely failed to improve survival. Combination chemotherapy is the standard treatment approach for osteosarcoma and Ewing's sarcoma, but outcomes are poor for patients with recurrent disease. In order to improve outcomes (in particular, progression-free survival [PFS] and overall survival [OS]), strategies shown to be effective in other solid malignancies, such as maintenance therapy and long-term treatment with targeted therapy, are being investigated in patients with advanced sarcomas. One potential promising approach is the use of mammalian target of rapamycin (mTOR) inhibitors for maintenance therapy. One such mTOR inhibitor, ridaforolimus (AP23573, MK-8669), is currently being evaluated in patients with advanced bone and STS in the ongoing Sarcoma mUlti-Center Clinical Evaluation of the Efficacy of riDaforolimus (SUCCEED) trial.     

An analysis of 117 cases of patients who died from tumor recurrence or from the progression of ovarian malignancies

Out of 403 patients with ovarian with malignancies during 1978 to, 1985, 117 (29.0%) died from the progression of a non-curative cancer (56 cases, 47.9%) or from a cancer recurrence (61 cases, 52.1%). The mean survival rate 117 cases was 13.4 months, of which 103 (88.0%) cases concerned patients who died within 2 years and 114 (97.4%) who died within 3 years. A histological analysis revealed that patients with a serous or an endometrial cancer had a longer survival rate than others. Among 61 recurrent cases, 59 (96.7%) fell into recurrence within 2 years. Regarding the relationship between a recurrent of cancer and its prognosis, patients with a recurrence of an ascitic or a metastatic disease had a poorer prognosis than patients with a pelvic or an abdominal mass. An aggressive operation, such as a resection of a recurrent tumor, even if small in volume, led to a better prognostic result than no therapy.     

Neoadjuvant chemotherapy for osteosarcoma of the extremities with metastases at presentation: recent experience at the Rizzoli Institute in 57 patients treated with cisplatin, doxorubicin, and a high dose of methotrexate and ifosfamide.

BACKGROUND: Effective adjuvant or neoadjuvant regimens of chemotherapy have dramatically improved the prognosis of patients with high-grade osteosarcoma of the extremity, localized at diagnosis. Currently, little is known about patients with metastatic disease at presentation. PATIENTS AND METHODS: From May 1995 to May 2000, 57 patients with osteosarcoma of the extremity, metastatic at presentation, were treated according to the following scheme: primary chemotherapy, restaging, simultaneous resection of primary tumor and metastatic lesions, and maintenance chemotherapy. RESULTS: Thirty-five patients achieved remission. At a follow-up ranging from 2 to 7 years, seven remained continuously free of disease, one died of chemotherapy-related toxicity and 27 patients relapsed. Twenty-one of the 22 patients who never achieved remission died as a result of the tumor, as well as 20 of the 27 who achieved remission but then relapsed. Of the remaining seven relapsing patients, six are alive with uncontrolled disease, while one is alive and free of disease 24 months after the last post-relapse treatment. Two-year event-free survival (EFS) and overall survival (OS) were 21% and 55%, respectively. These results are significantly poorer than those achieved in 128 contemporary patients with non-metastatic disease at presentation, treated with the same chemotherapy protocol (2-year EFS and OS of 75% and 94%, respectively). CONCLUSIONS: The results of our study confirm that the prognosis of patients with osteosarcoma of the extremity, metastatic at presentation, remains poor, despite the use of aggressive treatments.     

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours.

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.     

Curability of Ewing's sarcoma and considerations for future therapeutic trials

Twenty previously untreated children with primary Ewing's sarcoma and 8 children with primary tumor and metastatic disease were treated with surgery or radiation therapy (6,000-7,000 rads) for their primary tumor and T-2 chemotherapy. Of the 20 children with primary Ewing's sarcoma treated with T-2 "adjuvant" chemotherapy, 15 had no evidence of recurrent disease for from 31+-82+ months (median 46+ months) from the start of treatment. The actuarial 5-year disease-free survival rate for this group of patients was 75%. Eight patients presenting with metastatic disease had complete responses to T-2 chemotherapy, but 7/8 with metastatic disease eventually had tumor recurrence. Examination of the treatment failures, both those patients relapsing after adjuvant chemotherapy for primary Ewing's sarcoma (5), and those relapsing after having a complete response of metastatic disease (7) to T-2 chemotherapy, revealed that all relapses occurred at the end of the second year of T-2 chemotherapy or after chemotherapy was stopped. In addition, of 23 patients receiving "curative" radiation therapy to their primary tumor, 5 had local recurrence (22%) and 6 (26%) had severe functional debility secondary to combined radiation therapy and T-2 chemotherapy. The conclusions drawn from this experience have led us to consider a new approach to the treatment of Ewing's sarcoma, namely: 1) more aggressive initial or "induction" chemotherapy with subsequent T-2 "maintenance" chemotherapy to eradicate more completely all metastatic microfoci of disease presumed to be present in patients with primary tumor at the time of diagnosis, and ostensively present in patients with metastatic disease; 2) the use of surgery alone or in combination with moderate doses of radiation therapy in those patients in whom we can predict a high frequency of local recurrence (pelvic lesions) or a high percentage of "functional failures" (young children with lower extremity lesions). Preliminary results with this latter approach are encouraging with 11/13 patients with primary Ewing's sarcoma free of disease at 12+-26+ months. A longer follow-up of this more aggressive treatment is needed to determine the superiority of this approach for both increased survival and improved late physical rehabilitation.     

Preliminary results of treatment of Ewing's sarcoma of bone in children and young adults: six months of intensive combined modality therapy without maintenance

Thirty-one previously untreated patients with Ewing's sarcoma were treated with an intensive chemotherapy program of vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cyclosphosphamide (VADRIAC) in combination with radiation therapy to the primary site (greater than 50 Gy) and bone metastases (45 to 50 Gy). An intensified regimen with one further cycle of chemotherapy (VADRIAC), total body irradiation (TBI), and autologous bone marrow transplantation was given to patients with primary tumors of the pelvis, humerus, femur, and chest wall without metastases and to all patients with metastases at diagnosis. Patients with primary tumors of the distal extremity and other sites without metastases at diagnosis were treated on a less intensive chemotherapy regimen of VADRIAC without the intensification. Therapy was completed within 6 to 7 months in all patients. Thirteen patients had metastatic disease at diagnosis; only two of these had the lung as the sole site of metastatic disease. Eighteen patients had no evidence of metastatic disease at diagnosis: ten of these patients had tumors that arose in central axis and proximal extremity sites, and eight had tumors that arose in distal extremity and other sites. Thirty of the 31 patients achieved a complete remission, although two patients underwent amputation: one before chemotherapy and radiation and one after chemotherapy and radiation because of persistent local disease. Seventeen remain in their first complete remission at a median time on study of 30 months and a median time after completion of therapy of 24 months. Fourteen patients have relapsed (13) or progressed (1): ten in metastatic sites and four in the primary site. One patient had persistent local disease after radiation requiring amputation. Nine of the 13 patients with metastatic disease at diagnosis have relapsed compared with five of the 18 patients without metastatic disease. For the entire group, the actuarial survival is 78% (65% to 87%) at 30 months, and the actuarial disease-free survival is 58% (46% to 69%) at 30 months.     

Treatment of osteosarcoma at first recurrence after contemporary therapy: the Memorial Sloan-Kettering Cancer Center experience

BACKGROUND: Overall survival after recurrence of osteosarcoma (OS) is < 30%. The authors reported their experience treating recurrent OS at the time of first recurrence (R1). METHODS: Patients with high-grade OS who achieved complete disease remission (CR) after primary surgery and chemotherapy, and patients who were treated at R1 at Memorial Sloan-Kettering Cancer Center (New York, NY) after 1990 were analyzed by retrospective chart review. RESULTS: For 43 eligible patients, the median time to R1 from initial diagnosis was 21.7 months (range, 4.6-135.7 mos). The lungs were the most common sites of disease recurrence (n = 33 of 43). With a median follow-up of 15.2 months (range, 0.7-158.3 mos) after R1, 15 of 43 (35%) patients were alive. Four of 43 patients were treated with surgery alone (3 patients were alive and 1 had died of progressive disease at the time of last follow-up). Due to unresectable disease, eight patients received only chemotherapy, none of whom survived. For patients with disease recurrence treated with chemotherapy and surgery (n = 31), 22 patients achieved a second CR (CR2). Nine patients were alive and in disease remission (29%) at the time of last follow-up. Twenty-three patients received ifosfamide as part of their retrieval regimen. Of the 18 who achieved a CR2, 8 experienced disease recurrence, 7 remain alive in CR2, and 3 died due to toxicity. Eight patients did not receive ifosfamide. Of these, 4 achieved a CR2 but 3 subsequently experienced disease recurrence. CONCLUSIONS: At R1, 22 of 31 patients achieved a CR2 with aggressive surgery and chemotherapy. The majority of these patients subsequently developed a disease recurrence. Patients appeared to benefit from the addition of ifosfamide to their retrieval regimens. In the end, the role of chemotherapy in recurrent OS continues to remain undefined.     

Cisplatin-based chemotherapy in primary central nervous system germ cell tumors

We report a retrospective review of our experience with cisplatin-based chemotherapy in eight patients (ages 9–44 years) with histologically confirmed primary central nervous system germ cell tumors. Five patients received chemotherapy as the primary treatment, radiation therapy being administered either at completion of chemotherapy or between chemotherapy courses. Three patients received cisplatin-based chemotherapy for recurrent disease after prior radiation therapy and/or surgery. Four of five patients treated with chemotherapy at diagnosis are in complete remission at 11–14 months from diagnosis. The remaining patient twice achieved complete remission prior to dying of progressive disease 16 months after diagnosis. Two of three patients treated with chemotherapy for recurrent disease are in complete remission at 20 and 26 months; the remaining patient deteriorated after the first cycle of chemotherapy and expired six months thereafter. Overall, of seven patients evaluable for response, five achieved complete remission with chemotherapy alone, and two with chemotherapy and radiation therapy. Our results confirm previous reports of high complete remission rates utilizing cisplatin-based chemotherapy in conjunction with radiation therapy. Prospective evaluation of cisplatin-based chemotherapy followed by radiation therapy is warranted.     

Autologous bone marrow transplantation for adult poor-risk lymphoblastic lymphoma in first remission.

PURPOSE: Adult patients with poor-risk lymphoblastic lymphoma (LBL) treated with intensive multiagent chemotherapy (acute lymphoblastic leukemia [ALL]-like regimens) have a poor prognosis, with a disease-free long-term survival rate of less than 20%, caused by a very high relapse rate. Thus, adult patients with poor-risk LBL are candidates for alternative intensive consolidation therapy. PATIENTS AND METHODS: Nine adult patients with poor-risk LBL in first remission after treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; six patients) or ALL-like regimens (three patients), were treated with high-dose cyclophosphamide and total body irradiation (TBI) followed by nonpurged autologous bone marrow transplantation (ABMT). RESULTS: Two of nine patients relapsed at 4 and 8 months, respectively, after BMT, and one patient died of acute myeloblastic leukemia (AML) 7 months after ABMT without recurrence of his lymphoma. Six patients are in unmaintained first remission with a follow-up of 12 to 113 months (median, 53 months) after transplantation. CONCLUSIONS: These results suggest that intensive consolidation therapy with high-dose cyclophosphamide and TBI followed by nonpurged ABMT may improve the long-term prognosis of this disease.     

Primary oral etoposide therapy in gestational trophoblastic disease. An update

Sixty patients who developed persistent or metastatic gestational trophoblastic disease (GTD) received primary oral etoposide therapy (VP 16-213). Twelve patients had metastatic GTD. Fifty-nine patients achieved biochemical remission. One patient had marked nausea and vomiting and the therapy was switched to a methotrexate/folinic acid regimen. Three patients developed relapse of GTD, giving a relapse rate of 5.1%. Etoposide is an active drug against choriocarcinoma. Its use should not be restricted to drug-resistant GTD.     

Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome--the French pediatric experience

BACKGROUND: The objective of this report was to estimate long-term outcome and prognostic factors in children and adolescents who presented with metastatic osteosarcoma at diagnosis. Patients were treated in six French pediatric oncology centers with surgery and multiagent chemotherapy, mainly with high-dose methotrexate. Their medical records were reviewed retrospectively. METHODS: The medical records of patients who were treated for metastatic osteosarcoma from 1987 to 2000 were reviewed. Patients were treated with the chemotherapy regimens recommended for nonmetastatic disease in children (the French Society of Pediatric Oncology OS 87 and OS 94 protocols) or, in a few patients, with other chemotherapy regimens. Surgical excision of the primary tumor and, when possible, of all metastatic sites was performed based on a personalized assessment of each patient's situation. RESULTS: Seventy-eight patients age < 20 years were treated. Forty-six patients (59%) had only 1 metastatic site (35 to the lungs and 11 to bone). Twenty-eight patients (36%) achieved a complete remission after combination chemotherapy and surgery. The event-free survival and overall survival rates at 5 years were 14% and 19%, respectively. To date, 14 patients (18%) have remained alive with a median follow-up of 112 months. Pretreatment features associated with a shorter event-free survival in the multivariate analysis were metastasis to at least two organs and high alkaline phosphatase level. Patients with at least 1 of these poor prognostic factors had a 2.6% event-free survival rate at 5 years despite treatment. CONCLUSIONS: The survival of patients with metastatic osteosarcoma were treated with conventional chemotherapy and surgery remained very poor. Patients should be classified into different prognostic groups and treated accordingly. New therapeutic approaches are warranted to improve the prognosis for patients with the most severe disease.     

The effect of prior adjuvant chemotherapy on survival in metastatic breast cancer

Some adjuvantly treated patients develop recurrent breast cancer and little is known about the effect of prior adjuvant chemotherapy on subsequent response rates to systemic therapy or on overall survival. We describe our retrospective comparison of 179 patients who received doxorubicin containing adjuvant chemotherapy and developed recurrent breast cancer on University of Arizona Cancer Center clinical trials with 202 non-adjuvantly treated patients entered onto clinical protocols for recurrent or metastatic breast cancer during the same period. Adjuvant failures had a shorter median survival from the date of onset of recurrent disease (18 months versus 28 months, P less than 0.001), a lower response rate to initial combination chemotherapy (38% versus 69%, P = 0.001), and a high incidence of CNS involvement at the time of relapse (11%). In patients having recurrent or metastatic breast cancer, a history of prior adjuvant chemotherapy appears to identify a subgroup who will have a higher incidence of CNS involvement, a lower response rate to chemotherapy and a shorter survival with metastatic disease. These findings may help explain the failure of improved relapse free survival seen in many adjuvant chemotherapy trials to result in improved overall survival.